Laboratory of Retroviruses & Structural Biochemistry @ IBCP-MMSB

Research Highlights Collab. Publications Funding Equipment Team Servers

are characterized by their ability to gain resistance from therapeutic or vaccinal intervention through the accumulation of escape mutations in the viral genome and/or the interaction of regulatory viral proteins with cellular pathways. Understanding the structural determinants of the functions of the viral proteins is crucial for the development of efficient antiviral therapies.

Our research is conducted on both animal and human retroviruses and takes advantage of the presence in the Biodistrict Lyon-Gerland of the CIRI (International Center for Infectiology Research) and of the world-leading companies Merial-Boehringer and Sanofi, which are dedicated to animal and human health.
We study proteins, protein-ligand and protein-acid nucleic complexes by biochemical (chromatography, electrophoresis...), biophysical (magnetic-tweezers, SAXS...) and structural-atomic (X-ray crystallography, cryo-EM, in silico docking...) approaches.

Hence, our team has characterized the crystal structure of an epitope of the trans-activator Tat of the human virus HIV-1 in complex with its cognate antibody (Serrière et al., 2011

), observed a new dimeric form of an avian integrase domain (Ballandras et al., 2011

) and determined the crystal structures of the matrix and capsid proteins of the Feline Immunodeficiency Virus (FIV) (Serrière et al., 2013

; Folio et al., 2017

).

On-going projects on retroviral integrases aim to observe the concerted integration mechanism at the single molecule scale with magnetic tweezers (F. Fiorini in coll. with V. Parissi) and to make safer the use of pig tissues and organs in human xenotransplantation (P. Gouet, M. Chahpazoff in coll. with Y. Blanchard). In parallel, we investigate chromosomal targeting by integrase (X. Robert, P. Gouet in coll. with V. Parissi) and we seek to rationally develop a new class of protein-protein inhibitors against this enzyme (P. Gouet, X. Robert, F. Fiorini in coll. with C. Ronfort and L. Guy).

We also work on the molecular mechanisms underlying the biological function of the transactivating protein Tax from Human T-Lymphotropic Virus (HTLV), whose structure is unknown (C. Guillon, M. Dujardin in coll. with R. Mahieux and G. Schoehn). Tax is a modular protein with disordered regions and we use a structural biological integrative approach combining X-ray crystallography, NMR and cryo-EM.

Furthermore, we aim at the identification of therapeutic molecules targeting assembly of the capsid protein of FIV by a combination of in vitro screening, bio-guided design process and structural studies (C. Guillon in coll. with G. Álvarez Touron).

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We have a genuine interest for several non-viral therapeutic targets and we have carried out structural studies on taurocyamine kinases in trematodes (Merceron et al., 2015

, in coll. with O. Marcillat), the bacterial type 2 secretion system (Pineau et al., 2014

, in coll. with V. Shevchik) and the Ser/Thr kinase StkP of S. pneumoniae (Righino et al., 2017

, in coll. with MC. de Rosa; Zucchini et al., 2018

, in coll. with C. Grangeasse).

Finally, we have created the joint Web server ESPript

/ ENDscript

for protein sequence and structure analyses, which counts more than 15,000 users per year (Robert & Gouet, 2014

By clicking on the PDB logo, you will be redirected to the Protein Data Bank website presenting the extensive list of the structures we solved @IBCP.

Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein
Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.7 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tridimensional structure of a functional, full-length FIV CA. Folio C, Sierra N, Dujardin M, Alvarez G & Guillon C (2017). Viruses. 9:335

Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein

Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.7 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tridimensional structure of a functional, full-length FIV CA.

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Folio C, Sierra N, Dujardin M, Alvarez G & Guillon C (2017). Viruses. 9:335

Biophysical characterization and crystal structure of the Feline Immunodeficiency Virus p15 matrix protein
Our biochemical study of the p15 matrix protein of the Feline Immunodeficiency Virus (FIV) revealed that it forms a stable dimer in solution under acidic conditions and at high concentration, unlike other retroviral matrix proteins. We determined the crystal structure of full-length FIV p15 to 2 Å resolution and observed a helical organization of the protein, typical for retroviral matrix proteins. A hydrophobic pocket that could accommodate a myristoyl group was identified, and the C-terminal end of FIV p15, which is mainly unstructured, was visible in electron density maps. As FIV p15 crystallizes in acidic conditions but with one monomer in the asymmetric unit, we searched for the presence of a biological dimer in the crystal. No biological assembly was detected by the PISA server, but the three most buried crystallographic interfaces have interesting features: the first one displays a highly conserved tryptophan acting as a binding platform; the second one is located along a 2-fold symmetry axis and the third one resembles the dimeric interface of EIAV p15. Because the C-terminal end of p15 is involved in two of these three interfaces, we investigated the structure and assembly of a C-terminal-truncated form of p15 lacking 14 residues. The truncated FIV p15 dimerizes in solution at a lower concentration and crystallizes with two molecules in the asymmetric unit. The EIAV-like dimeric interface is the only one to be retained in the new crystal form and could therefore correspond to the one of FIV p15 in solution. Serrière J, Robert X, Perez M, Gouet P & Guillon C (2013). Retrovirology. 10:64

Biophysical characterization and crystal structure of the Feline Immunodeficiency Virus p15 matrix protein

Our biochemical study of the p15 matrix protein of the Feline Immunodeficiency Virus (FIV) revealed that it forms a stable dimer in solution under acidic conditions and at high concentration, unlike other retroviral matrix proteins. We determined the crystal structure of full-length FIV p15 to 2 Å resolution and observed a helical organization of the protein, typical for retroviral matrix proteins. A hydrophobic pocket that could accommodate a myristoyl group was identified, and the C-terminal end of FIV p15, which is mainly unstructured, was visible in electron density maps. As FIV p15 crystallizes in acidic conditions but with one monomer in the asymmetric unit, we searched for the presence of a biological dimer in the crystal. No biological assembly was detected by the PISA server, but the three most buried crystallographic interfaces have interesting features: the first one displays a highly conserved tryptophan acting as a binding platform; the second one is located along a 2-fold symmetry axis and the third one resembles the dimeric interface of EIAV p15. Because the C-terminal end of p15 is involved in two of these three interfaces, we investigated the structure and assembly of a C-terminal-truncated form of p15 lacking 14 residues. The truncated FIV p15 dimerizes in solution at a lower concentration and crystallizes with two molecules in the asymmetric unit. The EIAV-like dimeric interface is the only one to be retained in the new crystal form and could therefore correspond to the one of FIV p15 in solution.

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Serrière J, Robert X, Perez M, Gouet P & Guillon C (2013). Retrovirology. 10:64

A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly
Integrase (IN) is an important therapeutic target in the search for anti-Human Immunodeficiency Virus (HIV) inhibitors. This modular enzyme is hard to crystallize. A first structural result was obtained with the IN catalytic core domain (CCD) of the avian Rous Sarcoma Virus (RSV). A ribonuclease-H like motif was revealed as well as a dimeric interface stabilized by two pairs of α-helices. These structural features have been validated in other structures of IN CCDs. We have determined the crystal structure of the Rous-associated virus type-1 (RAV-1) IN CCD to 1.8 Å resolution. RAV-1 IN shows a standard activity for integration and its CCD differs in sequence from that of RSV by a single accessible residue in position 182 (substitution A182T). Surprisingly, the CCD of RAV-1 IN associates itself with an unexpected dimeric interface characterized by three pairs of α-helices. A182 is not involved in this novel interface, which results from a rigid body rearrangement of the protein at its dimeric surface. A new basic groove that is suitable for single-stranded nucleic acid binding is observed at the surface of the dimer. We have determined the structure of the mutant A182T of RAV-1 IN CCD and obtained a RSV IN CCD-like structure with two pairs of buried α-helices at the interface. Our results suggest that the CCD of avian INs can dimerize in more than one state. Such flexibility can further explain the multifunctionality of the retroviral IN, which beside integration of dsDNA is implicated in different steps of the retroviral cycle in presence of viral ssRNA. Ballandras A, Moreau K, Robert X, Confort MP, Merceron R, Haser R, Ronfort C & Gouet P (2011). PLoS One. 6:e23032

A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly

Integrase (IN) is an important therapeutic target in the search for anti-Human Immunodeficiency Virus (HIV) inhibitors. This modular enzyme is hard to crystallize. A first structural result was obtained with the IN catalytic core domain (CCD) of the avian Rous Sarcoma Virus (RSV). A ribonuclease-H like motif was revealed as well as a dimeric interface stabilized by two pairs of α-helices. These structural features have been validated in other structures of IN CCDs. We have determined the crystal structure of the Rous-associated virus type-1 (RAV-1) IN CCD to 1.8 Å resolution. RAV-1 IN shows a standard activity for integration and its CCD differs in sequence from that of RSV by a single accessible residue in position 182 (substitution A182T). Surprisingly, the CCD of RAV-1 IN associates itself with an unexpected dimeric interface characterized by three pairs of α-helices. A182 is not involved in this novel interface, which results from a rigid body rearrangement of the protein at its dimeric surface. A new basic groove that is suitable for single-stranded nucleic acid binding is observed at the surface of the dimer. We have determined the structure of the mutant A182T of RAV-1 IN CCD and obtained a RSV IN CCD-like structure with two pairs of buried α-helices at the interface. Our results suggest that the CCD of avian INs can dimerize in more than one state. Such flexibility can further explain the multifunctionality of the retroviral IN, which beside integration of dsDNA is implicated in different steps of the retroviral cycle in presence of viral ssRNA.

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Ballandras A, Moreau K, Robert X, Confort MP, Merceron R, Haser R, Ronfort C & Gouet P (2011). PLoS One. 6:e23032

The substrate-free and -bound crystal structures of the duplicated taurocyamine kinase from the human parasite Schistosoma mansoni
The taurocyamine kinase from the blood fluke Schistosoma mansoni (SmTK) belongs to the phosphagen kinase (PK) family and catalyzes the reversible Mg²⁺-dependent transfer of a phosphoryl group between ATP and taurocyamine. SmTK is derived from gene duplication, as are all known trematode TKs. Our crystallographic study of SmTK reveals the first atomic structure of both a TK and a PK with a bilobal structure. The two unliganded lobes present a canonical open conformation and interact via their respective C- and N-terminal domains at a helix-mediated interface. This spatial arrangement differs from that observed in true dimeric PKs, in which both N-terminal domains make contact. Our structures of SmTK complexed with taurocyamine or L-arginine compounds explain the mechanism by which an arginine residue of the phosphagen specificity loop is crucial for substrate specificity. A SmTK crystal was soaked with the dead-end transition state analog (TSA) components taurocyamine-NO₃^--MgADP. One SmTK monomer was observed with two bound TSAs and an asymmetric conformation, with the first lobe semiclosed and the second closed. However, isothermal titration calorimetry and enzyme kinetics experiments showed that the two lobes function independently. A small angle X-ray scattering model of SmTK-TSA in solution with two closed active sites was generated. Merceron R, Awama AM, Montserret R, Marcillat O & Gouet P (2015). J. Biol. Chem. 290:12951-63

The substrate-free and -bound crystal structures of the duplicated taurocyamine kinase from the human parasite Schistosoma mansoni

The taurocyamine kinase from the blood fluke Schistosoma mansoni (SmTK) belongs to the phosphagen kinase (PK) family and catalyzes the reversible Mg²⁺-dependent transfer of a phosphoryl group between ATP and taurocyamine. SmTK is derived from gene duplication, as are all known trematode TKs. Our crystallographic study of SmTK reveals the first atomic structure of both a TK and a PK with a bilobal structure. The two unliganded lobes present a canonical open conformation and interact via their respective C- and N-terminal domains at a helix-mediated interface. This spatial arrangement differs from that observed in true dimeric PKs, in which both N-terminal domains make contact. Our structures of SmTK complexed with taurocyamine or L-arginine compounds explain the mechanism by which an arginine residue of the phosphagen specificity loop is crucial for substrate specificity. A SmTK crystal was soaked with the dead-end transition state analog (TSA) components taurocyamine-NO₃^--MgADP. One SmTK monomer was observed with two bound TSAs and an asymmetric conformation, with the first lobe semiclosed and the second closed. However, isothermal titration calorimetry and enzyme kinetics experiments showed that the two lobes function independently. A small angle X-ray scattering model of SmTK-TSA in solution with two closed active sites was generated.

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Merceron R, Awama AM, Montserret R, Marcillat O & Gouet P (2015). J. Biol. Chem. 290:12951-63

Deciphering key features in protein structures with the new ENDscript server
ENDscript 2 is a friendly webserver for extracting and rendering a comprehensive analysis of primary to quaternary protein structure information in an automated way. This major upgrade has been fully re-engineered to enhance speed, accuracy and usability with interactive 3D visualization. It takes advantage of the new version 3 of ESPript, our well-known sequence alignment renderer, improved to handle a large number of data with reduced computation time. From a single PDB entry or file, ENDscript produces high quality figures displaying multiple sequence alignment of proteins homologous to the query, colored according to residue conservation. Furthermore, the experimental secondary structure elements and a detailed set of relevant biophysical and structural data are depicted. All this information and more are now mapped on interactive 3D PyMOL representations. Thanks to its adaptive and rigorous algorithm, beginner to expert users can modify settings to fine-tune ENDscript to their needs. ENDscript has also been upgraded as an open platform for the visualization of multiple biochemical and structural data coming from external biotool webservers, with both 2D and 3D representations. ENDscript 2 and ESPript 3 are freely available at https://endscript.ibcp.fr and https://espript.ibcp.fr . Robert X & Gouet P (2014). Nucleic Acids Res. 42:W320-4

Deciphering key features in protein structures with the new ENDscript server

ENDscript 2 is a friendly webserver for extracting and rendering a comprehensive analysis of primary to quaternary protein structure information in an automated way. This major upgrade has been fully re-engineered to enhance speed, accuracy and usability with interactive 3D visualization. It takes advantage of the new version 3 of ESPript, our well-known sequence alignment renderer, improved to handle a large number of data with reduced computation time. From a single PDB entry or file, ENDscript produces high quality figures displaying multiple sequence alignment of proteins homologous to the query, colored according to residue conservation. Furthermore, the experimental secondary structure elements and a detailed set of relevant biophysical and structural data are depicted. All this information and more are now mapped on interactive 3D PyMOL representations. Thanks to its adaptive and rigorous algorithm, beginner to expert users can modify settings to fine-tune ENDscript to their needs. ENDscript has also been upgraded as an open platform for the visualization of multiple biochemical and structural data coming from external biotool webservers, with both 2D and 3D representations. ENDscript 2 and ESPript 3 are freely available at https://endscript.ibcp.fr

and https://espript.ibcp.fr

Robert X & Gouet P (2014). Nucleic Acids Res. 42:W320-4

Internal IBCP
Vincent ChaptalMMSB, CNRS – Université de Lyon Christophe GrangeasseMMSB, CNRS – Université de Lyon Guillaume LaunayMMSB, CNRS – Université de Lyon Juliette MartinMMSB, CNRS – Université de Lyon Cédric OrelleMMSB, CNRS – Université de Lyon Bernard VerrierLBTI, CNRS – Université de Lyon

External
Guzmán Álvarez TouronUniversidad de la República - Paysandú, Uruguay Yannick BlanchardViral Genetics and Biosafety - ANSES Ploufragan, France Laure GuyÉcole Normale Supérieure - Lyon, France Xavier HanoulleNMR & Molecular Interactions - CNRS Villeneuve d'Ascq, France Vincent ParissiFundamental Microbiology and Pathogenicity Lab - CNRS Bordeaux, France Stéphane PaulGroupe sur l'Immunité des Muqueuses et Agents Pathogènes - Faculté de Médecine de Saint-Etienne, France Corinne RonfortPathogenicity and Virus Vaccine Lab - INRA Grenoble, France Maria-Cristina de RosaInstitute of Chemistry of Molecular Recognition - Rome, Italy Guy SchoehnInstitute of Structural Biology - Grenoble, France Vladimir ShevchikMicrobiology, Adaptation and Pathogenesis Lab - INSA Villeurbanne, France

External

Guzmán Álvarez TouronUniversidad de la República - Paysandú, Uruguay
Yannick BlanchardViral Genetics and Biosafety - ANSES Ploufragan, France
Laure GuyÉcole Normale Supérieure - Lyon, France
Xavier HanoulleNMR & Molecular Interactions - CNRS Villeneuve d'Ascq, France
Vincent ParissiFundamental Microbiology and Pathogenicity Lab - CNRS Bordeaux, France
Stéphane PaulGroupe sur l'Immunité des Muqueuses et Agents Pathogènes - Faculté de
Médecine de Saint-Etienne, France
Corinne RonfortPathogenicity and Virus Vaccine Lab - INRA Grenoble, France
Maria-Cristina de RosaInstitute of Chemistry of Molecular Recognition - Rome, Italy
Guy SchoehnInstitute of Structural Biology - Grenoble, France
Vladimir ShevchikMicrobiology, Adaptation and Pathogenesis Lab - INSA Villeurbanne, France

* Corresponding authors

• Research articles @IBCP

[2023] [2022] [2021] [2020] [2019] [2018] [2017] [2016] [2015] [2014] [2013] [2012] [2011] [2010] [2009] [2008] [2007] [2006] [2005] [2004] [2003] [2002] [Review & Proceedings] [Commercial licence]

[2023]

Mohamed BS, Nguyen MC, Wein S, Uttaro JP, Robert X, Violot S, Ballut L, Jugnarain V, Mathé C*, Cerdan R, Aghajari N and Peyrottes S* (2023) Purine containing carbonucleoside phosphonate analogues as novel chemotype for Plasmodium falciparum Inhibition. Eur. J. Med. Chem. 258:115581

Martin J, Robert X, Gouet P, Falson P and Chaptal V* (2023) Specific Xray diffraction patterns of membrane proteins caused by secondary structure collinearity. Biochim. Biophys. Acta Biomembr., 1865:184065

[2022]

Rocchi C, Louvat C, Miele AE, Batisse J, Guillon C, Ballut L, Lener D, Negroni M, Ruff M, Gouet P and Fiorini F* (2022) The HIV-1 Integrase C-Terminal Domain Induces TAR RNA Structural Changes Promoting Tat Binding Int. J. Mol. Sci., 23:13742

Rocchi C, Gouet P, Parissi V and Fiorini F* (2022) The C-Terminal Domain of HIV-1 Integrase: A Swiss Army Knife for the Virus? Viruses, 14:1397

Bayart C, Mularoni A, Hemmani N, Kerachni S, Jose J, Gouet P, Paladino J and Le Borgne M* (2022) Tetanus Toxin Fragment C: Structure, Drug Discovery Research and Production. Pharmaceuticals, 15:756

Alvarez G, van Pul L, Robert X, Artía Z, van Nuenen AC, Long M, Sierra N, Porcal W, Kootstra NA and Guillon C* (2022) Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo. BMC Pharmacol. Toxicol., 23:43

Deymier S, Louvat C, Fiorini F and Cimarelli A* (2022) ISG20: an enigmatic antiviral RNase targeting multiple viruses. FEBS Open Bio, 12:1096-1111

[2021]

Long M, Toesca J and Guillon C* (2021) Review and perspectives on the structure–function relationships of the Gag subunits of Feline Immunodeficiency Virus. Pathogens 10:1502

Rocchi C, Louvat C, Miele A, Batisse J, Guillon C, Ballut L, Lener D, Negroni M, Ruff M, Gouet P and Fiorini F* (2021) The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding. bioRxiv, 2021.10.21.465253

Zampieri V, Gobet A, Robert X, Falson P and Chaptal V* (2021) CryoEM reconstructions of membrane proteins solved in several amphipathic solvents, nanodisc, amphipol and detergents, yield amphipathic belts of similar sizes corresponding to a common ordered solvent layer. Biochim. Biophys. Acta Biomembr., 1863:183693

Violot S, Galisson F, Carrique L, Jugnarain V, Conchou L, Robert X, Thureau A, Helbert W, Aghajari N and Ballut L* (2021) Exploring molecular determinants of polysaccharide lyase family 6-1 enzyme activity. Glycobiology, 31:1557-1570

Long M, Cantrelle FX, Robert X, Boll E, Sierra N, Gouet P, Hanoulle X, Alvarez GI* and Guillon C* (2021) Identification of a Potential Inhibitor of the FIV p24 Capsid Protein and Characterization of Its Binding Site. Biochemistry, 60:1896-1908

Matiadis D, Saporiti T, Aguilera E, Robert X, Guillon C, Cabrera N, Pérez-Montfort R, Sagnou M and Alvarez GI* (2021) Pyrazol(in)e derivatives of curcumin analogs as a new class of anti-Trypanosoma cruzi agents. Future Med. Chem., 13:701-714

Pineau C, Guschinskaya N, Gonçalves IR, Ruaudel F, Robert X, Gouet P, Ballut L* and Shevchik VE* (2021) Structure-function analysis of pectate lyase Pel3 reveals essential facets of protein recognition by the bacterial type 2 secretion system. J. Biol. Chem., 296:100305

[2020]

Gayet R, Michaud E, Nicoli F, Chanut B, Paul M, Rochereau N, Guillon C, He Z, Papagno L, Bioley G, Corthesy B & Paul S* (2020) Impact of IgA isoforms on their ability to activate dendritic cells and to prime T cells. Eur. J. Immunol. 50:1295-1306

Ferraro F, Corvo I, Bergalli L, Ilarraz A, Cabrera M, Gil J, Susuki BM, Caffrey CR, Timson DJ, Robert X, Guillon C, Freire T & Álvarez G* (2020) Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity. Sci. Rep. 10:2587

[2019]

Gallay K, Blot G, Chahpazoff M, Yajjou-Hamalian H, Confort MP, De Boisseson C, Leroux A, Luengo C, Fiorini F, Lavigne M, Chebloune Y, Gouet P, Moreau K, Blanchard Y & Ronfort C* (2019) In vitro, in cellulo and structural characterizations of the interaction between the integrase of Porcine Endogenous Retrovirus A/C and proteins of the BET family. Virology 532:69-81

Mauro E, Lesbats P, Lapaillerie D, Chaignepain S, Maillot B, Oladosu O, Robert X, Fiorini F, Kieffer B, Bouaziz S, Gouet P, Ruff M & Parissi V* (2019) Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase. Nucleic Acids Res. 47(7):3607-3618

[2018]

Reille S, Garnier M, Robert X, Gouet P, Martin J & Launay G* (2018) Identification and visualization of protein binding regions with the ArDock server. Nucleic Acids Res. 46:W417-422

Robert X, Kassis J, Ceres N, Martin J, Sawaya MIR, Read RJ, Gouet P, Falson P & Chaptal V* (2018) Au courant computation of the PDB to audit diffraction anisotropy of soluble and membrane proteins. Data In Brief 19:753–757

Gowravaram M, Bonneau F, Kanaan J, Maciej VD, Fiorini F, Raj S, Croquette V, Le Hir H & Chakrabarti S* (2018) A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner. Nucleic Acids Res. 46(5):2648-2659

Sierra N, Folio C, Robert X, Long M, Guillon C* & Álvarez G* (2018). Looking for novel capsid protein multimerization inhibitors of Feline Immunodeficiency Virus. Pharmaceuticals. 11(3):E67

Fiorini F, Robin J, Kanaan J, Borowiak M, Croquette V, Le Hir H, Jalinot P & Mocquet V* (2018) HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition. Nat. Commun. 9:431

Zucchini L, Mercy C, Garcia P, Cluzel C, Gueguen-Chaignon V, Galisson F, Freton C, Guiral S, Brochier-Armanet C, Gouet P & Grangeasse C* (2018) PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae. Nat. Microbiol. 3:197-209

[2017]

Hodeib S, Raj S, Manosas M, Zhang W, Bagchi D, Ducos B, Fiorini F, Kanaan J, Le Hir H, Allemand JF, Bensimon D & Croquette V* (2017) A mechanistic study of helicases with magnetic traps. Protein Sci. 26:1314-1336

Folio C, Sierra N, Dujardin M, Álvarez G & Guillon C* (2017) Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline. Viruses 9:335

Robert X, Kassis-Sahyoun J, Ceres N, Martin J, Sawaya M, Read R, Gouet P, Falson P & Chaptal V* (2017) X-ray diffraction reveals the intrinsic difference in the physical properties of membrane and soluble proteins. Sci. Rep. 7:17013

Benleulmi M, Matysiak J, Robert X, Miskey C, Mauro E, Lapaillerie D, Lesbats P, Chaignepain S, Henriquez D, Calmels C, Oladosu O, Thierry E, Leon O, Lavigne M, Andreola M, Delelis O, Ivics Z, Ruff M, Gouet P & Parissi V* (2017) Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails. Retrovirology 14:54

Righino B, Galisson F, Pirolli D, Vitale S, Réty S, Gouet P & De Rosa M* (2017) Structural model of the full-length Ser/Thr protein kinase StkP from S. pneumoniae and its recognition of peptidoglycan fragments. J. Biomol. Struct. Dyn. 1-14

Verrier B, Paul S, Terrat C, Bastide L, Ensinas A, Phelip C, Chanut B, Bulens-Grassigny L, Jospin F & Guillon C* (2017) Exploiting Natural Cross-reactivity between Human Immunodeficiency Virus (HIV)-1 p17 Protein and Anti-gp41 2F5 Antibody to Induce HIV-1 Neutralizing Responses In Vivo. Front. Immunol. 8:770. doi: 10.3389/fimmu.2017.00770

Shi J, Chen WF, Zhang B, Fan SH, Ai X, Liu NN, Réty S* & Xi XG (2017) A helical bundle in the N-terminal domain of the BLM helicase mediates dimer and potentially hexamer formation. J Biol Chem. 292:5909-20

[2016]

Chen WF, Dai YX, Duan XL, Liu NN, Shi W, Li N, Li M, Dou SX, Dong YH, Réty S* & Xi XG* (2016) Crystal structures of the BsPif1 helicase reveal that a major movement of the 2B SH3 domain is required for DNA unwinding. Nucleic Acids Res. 44:2949-61

[2015]

Demange A, Yajjou-Hamalian H, Gallay K, Luengo C, Beven V, Leroux A, Confort MP, Al Andary E, Gouet P, Moreau K, Ronfort C* & Blanchard Y* (2015). Porcine Endogenous Retrovirus (PERV)-A/C: biochemical properties of its Integrase and susceptibility to Raltegravir. J Gen Virol. 96:3124-30

Merceron R, Awama AM, Montserret R, Marcillat O* & Gouet P* (2015). The substrate-free and -bound crystal structures of the duplicated taurocyamine kinase from the human parasite Schistosoma mansoni. J Biol Chem. 290:12951-63

[2014]

Guillon C*, Bigouagou UM, Folio C, Jeannin P, Delneste Y & Gouet P (2014). A staggered decameric assembly of human C-reactive protein stabilized by zinc ions revealed by X-ray crystallography. Protein Pept Lett. 22:248-55

Pineau C, Guschinskaya N, Robert X, Gouet P, Ballut L* & Shevchik VE* (2014). Substrate recognition by the bacterial type II secretion system: more than a simple interaction. Mol Microbiol. 94:126-40

Robert X & Gouet P* (2014). Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42:W320-4

[2013]

Hassan S, Shevchik VE*, Robert X & Hugouvieux-Cotte-Pattat N (2013). PelN is a new pectate lyase of Dickeya dadantii with unusual characteristics. J Bacteriol. 195:2197-206

Lallemand M, Login FH, Guschinskaya N, Pineau C, Effantin G, Robert X & Shevchik VE* (2013). Dynamic interplay between the periplasmic and transmembrane domains of GspL and GspM in the type II secretion system. PLoS One 8:e79562-e79562

Serrière J, Robert X, Perez M, Gouet P & Guillon C* (2013). Biophysical characterization and crystal structure of the Feline Immunodeficiency Virus p15 matrix protein. Retrovirology. 10:64

Cellier C, Moreau K, Gallay K, Ballandras A, Gouet P & Ronfort C* (2013). In vitro functional analyses of the human immunodeficiency virus type 1 (HIV-1) integrase mutants give new insights into the intasome assembly. Virology. 439:97-104

Serrière J, Fenel D, Schoehn G, Gouet P & Guillon C* (2013). Biophysical characterization of the feline immunodeficiency virus p24 capsid protein conformation and in vitro capsid assembly. PLoS One. 8:e56424

[2012]

Merceron R, Foucault M, Haser R, Mattes R, Watzlawick H* & Gouet P* (2012). The molecular mechanism of thermostable α-galactosidases AgaA and AgaB explained by X-ray crystallography and mutational studies. J Biol Chem. 287:39642-52

[2011]

Ballandras A, Moreau K, Robert X, Confort MP, Merceron R, Haser R, Ronfort C* & Gouet P* (2011). A crystal structure of the catalytic core Domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly. PloS One. 6:e23032

Serrière J, Dugua JM, Bossus M, Vérrier B, Haser R, Gouet P & Guillon C* (2011). Fab'-induced folding of antigenic N-terminal peptides from intrinsically disordered HIV-1 Tat revealed by X-ray crystallography. J Mol Biol. 405:33-42

Charmetant J, Moreau K, Gallay K, Ballandras A, Gouet P & Ronfort C* (2011). Functional analyses of mutants of the central core domain of an Avian Sarcoma/Leukemia Virus integrase. Virology. 421:42-50

[2010]

Paracuellos P, Ballandras A, Robert X, Kahn R, Hervé M, Mengin-Lecreulx D, Cozzone AJ, Duclos B & Gouet P* (2010). The extended conformation of the 2.9-Å crystal structure of the three-PASTA domain of a Ser/Thr kinase from the human pathogen Staphylococcus aureus. J Mol Biol. 404:847-58

Foucault M, Mayol K, Receveur-Bréchot V, Bussat MC, Klinguer-Hamour C, Vérrier B, Beck A, Haser R, Gouet P & Guillon C* (2010). UV and X-ray structural studies of a 101-residue long Tat protein from a HIV-1 primary isolate and of its mutated, detoxified, vaccine candidate. Proteins. 78:1441-56

[2009]

Paracuellos P, Ballandras A, Robert X, Cozzone AJ, Duclos B & Gouet P* (2009). Crystallization and initial X-ray diffraction study of the three PASTA domains of the Ser/Thr kinase Stk1 from the human pathogen Staphylococcus aureus. Acta Crystallogr Sect F. 65:1187-9

Andreoletti P*, Mouesca JM, Gouet P, Jaquinod M, Capeillère-Blandin C & Jouve HM (2009). Verdoheme formation in Proteus mirabilis catalase. Biochim Biophys Acta. 1790:741-53

[2008]

Awama AM, Paracuellos P, Laurent S, Dissous C, Marcillat O & Gouet P* (2008). Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase. Acta Crystallogr Sect F. 64:854-7

Crézé C, Castang S, Dérivery E, Haser R, Hugouvieux-Cotte-Pattat N, Shevchik VE & Gouet P* (2008). The crystal structure of pectate lyase pelI from soft rot pathogen Erwinia chrysanthemi in complex with its substrate. J Biol Chem. 283:18260-8

Rakotobe D, Violot S, Hong SS, Gouet P & Boulanger P* (2008). Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed β-propeller domain of the HIV-1 cellular interactor EED. Virol J. 27;5:32

[2007]

Soulat D, Jault JM, Geourjon C, Gouet P, Cozzone AJ & Grangeasse C* (2007). Tyrosine-kinase Wzc from Escherichia coli possesses an ATPase activity regulated by autophosphorylation. FEMS Microbiol Lett. 274:252-9

Stephanidis B, Adichtchev S, Gouet P, McPherson A & Mermet A* (2007). Elastic properties of viruses. Biophys J. 93:1354-9

Crézé C, Rinaldi B, Haser R, Bouvet P & Gouet P* (2007). Structure of a d(TGGGGT) quadruplex crystallized in the presence of Li+ ions. Acta Crystallogr D. 63:682-8

[2006]

Castang S, Reverchon S, Gouet P & Nasser W* (2006). Direct evidence for the modulation of the activity of the Erwinia chrysanthemi quorum-sensing regulator ExpR by acylhomoserine lactone pheromone. J Biol Chem. 281:29972-87

Foucault M, Watzlawick H, Mattes R, Haser R & Gouet P* (2006). Crystallization and preliminary X-ray diffraction studies of two thermostable α-galactosidases from glycoside hydrolase family 36. Acta Crystallogr Sect F. 62:100-3

[2004]

Castang S, Chantegrel B, Deshayes C, Dolmazon R, Gouet P, Haser R, Reverchon S, Nasser W, Hugouvieux-Cotte-Pattat N & Doutheau A* (2004). N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing. Bioorg Med Chem Lett. 14:5145-9

Moreau K, Faure C, Violot S, Gouet P, Verdier G & Ronfort C* (2004). Mutational analyses of the core domain of Avian Leukemia and Sarcoma Viruses integrase: critical residues for concerted integration and multimerization. Virology. 318:566-81

Castang S, Shevchik VE, Hugouvieux-Cotte-Pattat N, Legrand P, Haser R & Gouet P* (2004). Crystallization of the pectate lyase PelI from Erwinia chrysanthemi and SAD phasing of a gold derivative. Acta Crystallogr D. 60:190-2

[2003]

Andreoletti P, Pernoud A, Sainz G, Gouet P & Jouve HM* (2003). Structural studies of Proteus mirabilis catalase in its ground state, oxidized state and in complex with formic acid. Acta Crystallogr D. 59:2163-8

Gouet P*, Robert X & Courcelle E (2003). ESPript/ENDscript: Extracting and rendering sequence and 3D information from atomic structures of proteins. Nucleic Acids Res. 31:3320-3

[2002]

Gouet P* & Courcelle E (2002). ENDscript: a workflow to display sequence and structure information. Bioinformatics. 18:767-8

• Review & Proceedings

Marcillat O, Laurent S, Awama A, Paracuellos P & Gouet P* (2009). "Structure of the Schistosoma mansoni guanidino kinase." FEBS J. 276:151-152 (Proceedings)

Gouet P* (2005). « L'exemple de la détermination de la structure cristallographique de la nucléocapside du bluetongue virus. » J Phys IV France. 130:203-207 (Review)

• Commercial licence

CNRS Commercial license DV 62804 for the webserver ESPript/ENDscript

Biochemistry room 1	Biochemistry room 2	FPLC system 1
FPLC system 2	DLS system	Crystallization robot
Microscopes room	Magnetic tweezers setup	Magnetic tweezers setup
$X-ray diffraction setup$ X-ray diffraction setup	Cryo data collection	Calculation servers

Pierre-Damien COUREUX PR Univ. Lyon 1	Francesca FIORINI CR CNRS	Francine GERARD-BARAGGIA MC Univ. Lyon 1
Patrice GOUET PR Univ. Lyon 1	Christophe GUILLON CR CNRS	Xavier ROBERT IR CNRS

Team:Retroviruses and Structural
Biochemistry

Head:Pr. Patrice GOUET

Titles:Professor of Structural Biology,
Group Head / PI

Location:Institut de Biologie et Chimie des
Protéines, 7 passage du Vercors,
F-69367 Lyon cedex 07, France

Contact:patrice.gouet@ibcp.fr
+33(0)4.72.72.26.24