Hiv env proteins
From Proteopedia
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| - | <StructureSection load='3dnn' size='400' side='right' caption=' | + | <StructureSection load='3dnn' size='400' side='right' caption='Molecular structure for the HIV-1 gp120 trimer in the unliganded state (PDB entry [[3dnn]])' scene=''> |
== Introduction == | == Introduction == | ||
Human Immunodeficiency Virus (HIV) is a retrovirus/lentivirus that expresses a spike protein on its viral envelope (Env). "The envelope protein is synthesized as a precursor, gp160, which trimerizes and undergoes cleavage into two noncovalently associated fragments, the receptor-binding fragment gp120 and the fusion fragment gp41" <ref name=Guan>PMID: 21076402 </ref>. Thus, Env is a heterodimer consisting of gp120 and gp41 and forms trimers on the surface of the viral membrane. As "the sole antigen on the virion surface," an understanding of Env (gp 120 & 41) and the conformational changes that occur in gp120 and gp41 during binding and fusion, respectively, is necessary in developing new fusion inhibitors and possible vaccines <ref name=Guan>PMID: 21076402 </ref> <ref name=Nick>PMID: 18668044 </ref>. The protein structure shown on the right is the gp120 portion of Env in its unbound trimer state <ref name=Nick>PMID: 18668044 </ref>. | Human Immunodeficiency Virus (HIV) is a retrovirus/lentivirus that expresses a spike protein on its viral envelope (Env). "The envelope protein is synthesized as a precursor, gp160, which trimerizes and undergoes cleavage into two noncovalently associated fragments, the receptor-binding fragment gp120 and the fusion fragment gp41" <ref name=Guan>PMID: 21076402 </ref>. Thus, Env is a heterodimer consisting of gp120 and gp41 and forms trimers on the surface of the viral membrane. As "the sole antigen on the virion surface," an understanding of Env (gp 120 & 41) and the conformational changes that occur in gp120 and gp41 during binding and fusion, respectively, is necessary in developing new fusion inhibitors and possible vaccines <ref name=Guan>PMID: 21076402 </ref> <ref name=Nick>PMID: 18668044 </ref>. The protein structure shown on the right is the gp120 portion of Env in its unbound trimer state <ref name=Nick>PMID: 18668044 </ref>. | ||
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== gp120 Binding == | == gp120 Binding == | ||
| - | gp120 is responsible for the binding of HIV to CD4 cells. "Binding of gp120 to the primary receptor CD4 and coreceptor (for example, CCR5 and CXCR4) induces large conformational changes, which then trigger dissociation of gp120 and a cascade of refolding events in gp41" <ref name=Guan>PMID: 21076402 </ref>. | + | gp120 is responsible for the binding of HIV to CD4 cells. "Binding of gp120 to the primary receptor CD4 and coreceptor (for example, CCR5 and CXCR4) induces large conformational changes, which then trigger dissociation of gp120 and a cascade of refolding events in gp41" <ref name=Guan>PMID: 21076402 </ref>. In the unliganded state, the <scene name='Sandbox/Gp120_v1_v2_loops/1'>V1/V2 loops</scene> are located at the center of the apex of the trimer. However, in the <scene name='Sandbox/Gp120_v1_v2_loops/2'>CD4 bound state</scene>, the V1/V2 loops undergo an outward rotational change that expose the central gp41 proteins at the base of the Env protein. |
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Revision as of 06:19, 27 November 2012
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References
- ↑ 1.0 1.1 1.2 1.3 Frey G, Chen J, Rits-Volloch S, Freeman MM, Zolla-Pazner S, Chen B. Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies. Nat Struct Mol Biol. 2010 Dec;17(12):1486-91. Epub 2010 Nov 14. PMID:21076402 doi:10.1038/nsmb.1950
- ↑ 2.0 2.1 2.2 Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S. Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008 Sep 4;455(7209):109-13. Epub 2008 Jul 30. PMID:18668044 doi:10.1038/nature07159
