X-Ray Structures of the Hexameric Building Block of the HIV Capsid

Journal Article · Fri Sep 11 04:00:00 EDT 2009 · Cell

DOI:https://doi.org/10.1016/j.cell.2009.04.063· OSTI ID:1005736

Pornillos, Owen; Ganser-Pornillos, Barbie K; Kelly, Brian N; Hua, Yuanzi; Whitby, Frank G; Stout, C David; Sundquist, Wesley I; Hill, Christopher P; Yeager, Mark

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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005736
• Journal Information: Cell, Journal Name: Cell Journal Issue: (7) ; 06, 2009 Vol. 137; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AIDS VIRUS
DESIGN
ENZYMES
FULLERENES
RESOLUTION