2ny6
From Proteopedia
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| - | [[Image:2ny6.gif|left|200px]]<br /> | + | [[Image:2ny6.gif|left|200px]]<br /><applet load="2ny6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ny6" size=" | + | |
caption="2ny6, resolution 2.80Å" /> | caption="2ny6, resolution 2.80Å" /> | ||
'''HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T123C, T257S, V275C,S334A, S375W, Q428C, G431C) Complexed with CD4 and Antibody 17b'''<br /> | '''HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T123C, T257S, V275C,S334A, S375W, Q428C, G431C) Complexed with CD4 and Antibody 17b'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The remarkable diversity, glycosylation and conformational flexibility of | + | The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: CD4 lymphocyte deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186940 186940]], Lupus erythematosus, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186940 186940]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2NY6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with NAG and SUC as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2NY6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=SUC:'>SUC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NY6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Arthos, J.]] | [[Category: Arthos, J.]] | ||
| - | [[Category: Burton, D | + | [[Category: Burton, D R.]] |
[[Category: Dey, B.]] | [[Category: Dey, B.]] | ||
| - | [[Category: Dimitrov, D | + | [[Category: Dimitrov, D S.]] |
| - | [[Category: Hessell, A | + | [[Category: Hessell, A J.]] |
| - | [[Category: Kwong, P | + | [[Category: Kwong, P D.]] |
| - | [[Category: Nabel, G | + | [[Category: Nabel, G J.]] |
| - | [[Category: Ryk, D | + | [[Category: Ryk, D Van.]] |
[[Category: Sodroski, J.]] | [[Category: Sodroski, J.]] | ||
[[Category: Wyatt, R.]] | [[Category: Wyatt, R.]] | ||
| - | [[Category: Xiang, S | + | [[Category: Xiang, S H.]] |
[[Category: Xu, L.]] | [[Category: Xu, L.]] | ||
[[Category: Yang, X.]] | [[Category: Yang, X.]] | ||
| - | [[Category: Zhang, M | + | [[Category: Zhang, M Y.]] |
[[Category: Zhou, T.]] | [[Category: Zhou, T.]] | ||
| - | [[Category: Zwick, M | + | [[Category: Zwick, M B.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: SUC]] | [[Category: SUC]] | ||
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[[Category: hiv]] | [[Category: hiv]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:12:23 2008'' |
Revision as of 16:12, 21 February 2008
|
HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T123C, T257S, V275C,S334A, S375W, Q428C, G431C) Complexed with CD4 and Antibody 17b
Contents |
Overview
The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.
Disease
Known diseases associated with this structure: CD4 lymphocyte deficiency OMIM:[186940], Lupus erythematosus, susceptibility to OMIM:[186940]
About this Structure
2NY6 is a Single protein structure of sequence from Homo sapiens and Human immunodeficiency virus 1 with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural definition of a conserved neutralization epitope on HIV-1 gp120., Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang SH, Yang X, Zhang MY, Zwick MB, Arthos J, Burton DR, Dimitrov DS, Sodroski J, Wyatt R, Nabel GJ, Kwong PD, Nature. 2007 Feb 15;445(7129):732-7. PMID:17301785
Page seeded by OCA on Thu Feb 21 18:12:23 2008
Categories: Homo sapiens | Human immunodeficiency virus 1 | Single protein | Arthos, J. | Burton, D R. | Dey, B. | Dimitrov, D S. | Hessell, A J. | Kwong, P D. | Nabel, G J. | Ryk, D Van. | Sodroski, J. | Wyatt, R. | Xiang, S H. | Xu, L. | Yang, X. | Zhang, M Y. | Zhou, T. | Zwick, M B. | NAG | SUC | Antibody | Cd4 | Gp120 | Hiv
