1g9m
From Proteopedia
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'''HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B''' | '''HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B''' | ||
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[[Category: Sweet, R W.]] | [[Category: Sweet, R W.]] | ||
[[Category: Wyatt, R.]] | [[Category: Wyatt, R.]] | ||
| - | [[Category: | + | [[Category: Antigen-binding fragment of human immunoglobulin 17b]] |
| - | [[Category: | + | [[Category: Hiv-1 exterior envelope gp120 from laboratory-adapted isolate]] |
| - | + | [[Category: Hxbc2]] | |
| - | [[Category: | + | [[Category: Surface t-cell glycoprotein cd4]] |
| - | [[Category: | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:19:06 2008'' |
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:19, 2 May 2008
HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B
Overview
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 Structure
1G9M is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Fri May 2 17:19:06 2008
Categories: Homo sapiens | Human immunodeficiency virus 1 | Protein complex | Hendrickson, W A. | Kwong, P D. | Majeed, S. | Robinson, J. | Sodroski, J. | Sweet, R W. | Wyatt, R. | Antigen-binding fragment of human immunoglobulin 17b | Hiv-1 exterior envelope gp120 from laboratory-adapted isolate | Hxbc2 | Surface t-cell glycoprotein cd4
