2nxz: Difference between revisions

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[[Image:2nxz.gif|left|200px]]<br />
[[Image:2nxz.gif|left|200px]]<br /><applet load="2nxz" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="2nxz" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="2nxz, resolution 2.04&Aring;" />
caption="2nxz, resolution 2.04&Aring;" />
'''HIV-1 gp120 Envelope Glycoprotein (T257S, S334A, S375W) Complexed with CD4 and Antibody 17b'''<br />
'''HIV-1 gp120 Envelope Glycoprotein (T257S, S334A, S375W) Complexed with CD4 and Antibody 17b'''<br />


==Overview==
==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.
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:[[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==
2NXZ 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, SUC, EDO, HEZ and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2NXZ OCA].  
2NXZ 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>, <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=EDO:'>EDO</scene>, <scene name='pdbligand=HEZ:'>HEZ</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NXZ OCA].  


==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Arthos, J.]]
[[Category: Arthos, J.]]
[[Category: Burton, D.R.]]
[[Category: Burton, D R.]]
[[Category: Dey, B.]]
[[Category: Dey, B.]]
[[Category: Dimitrov, D.S.]]
[[Category: Dimitrov, D S.]]
[[Category: Hessell, A.J.]]
[[Category: Hessell, A J.]]
[[Category: Kwong, P.D.]]
[[Category: Kwong, P D.]]
[[Category: Nabel, G.J.]]
[[Category: Nabel, G J.]]
[[Category: Ryk, D.Van.]]
[[Category: Ryk, D Van.]]
[[Category: Sodroski, J.]]
[[Category: Sodroski, J.]]
[[Category: Wyatt, R.]]
[[Category: Wyatt, R.]]
[[Category: Xiang, S.H.]]
[[Category: Xiang, S H.]]
[[Category: Xu, L.]]
[[Category: Xu, L.]]
[[Category: Yang, X.]]
[[Category: Yang, X.]]
[[Category: Zhang, M.Y.]]
[[Category: Zhang, M Y.]]
[[Category: Zhou, T.]]
[[Category: Zhou, T.]]
[[Category: Zwick, M.B.]]
[[Category: Zwick, M B.]]
[[Category: EDO]]
[[Category: EDO]]
[[Category: HEZ]]
[[Category: HEZ]]
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[[Category: hiv]]
[[Category: hiv]]


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