Nature Structural & Molecular Biology
12, 678 - 682 (2005)
Published online: 24 July 2005; | doi:10.1038/nsmb967
The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitorFrançois Ternois1, Jana Sticht2, Stéphane Duquerroy1, Hans-Georg Kräusslich2
& Félix A Rey1, 31
Laboratoire de Virologie Moléculaire & Structurale, UMR 2472/1157 CNRS-INRA and IFR 115, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. 2
Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany. 3
Virology Department, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
Correspondence should be addressed to Félix A Rey rey@vms.cnrs-gif.fr 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-Å-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  -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.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
