1g9m

File:1g9m.gif

spinqualitylabelsall models 1g9m, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B

OverviewOverview

BACKGROUND: The gp120 exterior envelope glycoprotein of HIV-1 binds, sequentially to CD4 and chemokine receptors on cells to initiate virus, entry. During natural infection, gp120 is a primary target of the humoral, immune response, and it has evolved to resist antibody-mediated, neutralization. We previously reported the structure at 2.5 A of a gp120, core from the HXBc2 laboratory-adapted isolate in complex with a 2 domain, fragment of CD4 and the antigen binding fragment of a human antibody. This, revealed atomic details of gp120-receptor interactions and suggested, multiple mechanisms of immune evasion. RESULTS: We have now extended the, HXBc2 structure in P222, crystals to 2.2 A. The enhanced resolution, enabled a more accurate modeling of less-well-ordered regions and provided, conclusive identification of the density in the central cavity at the crux, of the gp120-CD4 interaction as isopropanol from the crystallization, medium. We have also determined the structure of a gp120 core from the, primary clinical HIV-1 isolate, YU2, in the same ternary complex but in a, C2 crystal lattice. Comparisons of HXBc2 and YU2 showed that while CD4, binding was rigid, portions of the gp120 core were conformationally, flexible; overall differences were minor, with sequence changes, concentrated on a surface expected to be exposed on the envelope oligomer., CONCLUSIONS: Despite dramatic antigenic differences between primary and, laboratory-adapted HIV-1, the gp120 cores from these isolates are, remarkably similar. Taken together with chimeric substitution and sequence, analysis, this indicates that neutralization resistance is specified by, quaternary interactions involving the major variable loops and thus, affords a mechanism for viral adaptation. Conservation of the central, cavity suggests the possibility of therapeutic inhibitors. The structures, reported here extend in detail and generality our understanding of the, biology of the gp120 envelope glycoprotein.

About this StructureAbout this Structure

1G9M is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1 with NDG, NAG and IPA as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates., Kwong PD, Wyatt R, Majeed S, Robinson J, Sweet RW, Sodroski J, Hendrickson WA, Structure. 2000 Dec 15;8(12):1329-39. PMID:11188697

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