1g9m
From Proteopedia
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| - | [[Image:1g9m.gif|left|200px]]<br /> | + | [[Image:1g9m.gif|left|200px]]<br /><applet load="1g9m" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1g9m" size=" | + | |
caption="1g9m, resolution 2.2Å" /> | caption="1g9m, resolution 2.2Å" /> | ||
'''HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B'''<br /> | '''HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The gp120 exterior envelope glycoprotein of HIV-1 binds | + | 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. |
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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== | ||
| - | 1G9M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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 NDG, NAG and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1G9M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=NDG:'>NDG</scene>, <scene name='pdbligand=NAG:'>NAG</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=1G9M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hendrickson, W | + | [[Category: Hendrickson, W A.]] |
| - | [[Category: Kwong, P | + | [[Category: Kwong, P D.]] |
[[Category: Majeed, S.]] | [[Category: Majeed, S.]] | ||
[[Category: Robinson, J.]] | [[Category: Robinson, J.]] | ||
[[Category: Sodroski, J.]] | [[Category: Sodroski, J.]] | ||
| - | [[Category: Sweet, R | + | [[Category: Sweet, R W.]] |
[[Category: Wyatt, R.]] | [[Category: Wyatt, R.]] | ||
[[Category: IPA]] | [[Category: IPA]] | ||
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[[Category: surface t-cell glycoprotein cd4]] | [[Category: surface t-cell glycoprotein cd4]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:47:42 2008'' |
Revision as of 10:47, 21 February 2008
|
HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B
Contents |
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.
Disease
Known diseases associated with this structure: CD4 lymphocyte deficiency OMIM:[186940], Lupus erythematosus, susceptibility to OMIM:[186940]
About this Structure
1G9M is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1 with , and as ligands. 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 Thu Feb 21 12:47:42 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. | IPA | NAG | NDG | Antigen-binding fragment of human immunoglobulin 17b | Complex (hiv envelope protein/cd4/fab) | Hiv-1 exterior envelope gp120 from laboratory-adapted isolate | Hxbc2 | Surface t-cell glycoprotein cd4
