title: The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor.
abstract: Immature HIV particles bud from infected cells after assembly at the cytoplasmic side of cellular membranes. This assembly is driven by interactions between Gag polyproteins. Mature particles, each containing a characteristic conical core, are later generated by proteolytic maturation of Gag in the virion. The C-terminal domain of the HIV-1 capsid protein (C-CA) has been shown to contain oligomerization determinants essential for particle assembly. Here we report the 1.7-A-resolution crystal structure of C-CA in complex with a peptide capable of inhibiting immature- and mature-like particle assembly in vitro. The peptide inserts as an amphipathic alpha-helix into a conserved hydrophobic groove of C-CA, resulting in formation of a compact five-helix bundle with altered dimeric interactions. This structure thus reveals the details of an allosteric site in the HIV capsid protein that can be targeted for antiviral therapy.
authors.affiliation: Laboratoire de Virologie Moléculaire & Structurale, UMR 2472/1157 CNRS-INRA and IFR 115, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Ternois
authors.forename: Jana
authors.initials: J
authors.lastname: Sticht
authors.forename: Stéphane
authors.initials: S
authors.lastname: Duquerroy
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
authors.forename: Félix A
authors.initials: FA
authors.lastname: Rey
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019065:Virus Assembly / Q000235:genetics* / Q000502:physiology; D014961:X-Ray Diffraction
chemical_list: D036022:Capsid Proteins; D015683:Gene Products, gag; D046912:Multiprotein Complexes; D010455:Peptides