title: X-ray structures of the hexameric building block of the HIV capsid.
abstract: The mature capsids of HIV and other retroviruses organize and package the viral genome and its associated enzymes for delivery into host cells. The HIV capsid is a fullerene cone: a variably curved, closed shell composed of approximately 250 hexamers and exactly 12 pentamers of the viral CA protein. We devised methods for isolating soluble, assembly-competent CA hexamers and derived four crystallographically independent models that define the structure of this capsid assembly unit at atomic resolution. A ring of six CA N-terminal domains form an apparently rigid core, surrounded by an outer ring of C-terminal domains. Mobility of the outer ring appears to be an underlying mechanism for generating the variably curved lattice in authentic capsids. Hexamer-stabilizing interfaces are highly hydrated, and this property may be key to the formation of quasi-equivalent interactions within hexamers and pentamers. The structures also clarify the molecular basis for capsid assembly inhibition and should facilitate structure-based drug design strategies.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Owen
authors.initials: O
authors.lastname: Pornillos
authors.forename: Barbie K
authors.initials: BK
authors.lastname: Ganser-Pornillos
authors.forename: Brian N
authors.initials: BN
authors.lastname: Kelly
authors.forename: Yuanzi
authors.initials: Y
authors.lastname: Hua
authors.forename: Frank G
authors.initials: FG
authors.lastname: Whitby
authors.forename: C David
authors.initials: CD
authors.lastname: Stout
authors.forename: Wesley I
authors.initials: WI
authors.lastname: Sundquist
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Hill
authors.forename: Mark
authors.initials: M
authors.lastname: Yeager
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011108:Polymers / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D036022:Capsid Proteins; D011108:Polymers