3P30

crystal structure of the cluster II Fab 1281 in complex with HIV-1 gp41 ectodomain

Summary for 3P30

• Entry DOI: 10.2210/pdb3p30/pdb
• Descriptor: HIV-1 gp41, 1281 Fab light chain, 1281 Fab heavy chain (3 entities in total)
• Functional Keywords: hiv, gp41, cluster 2, fab, 6-helix bundle, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 57777.54

Authors

Frey, G.,Chen, J.,Rits-Volloch, S.,Freeman, M.M.,Zolla-Pazner, S.,Chen, B. (deposition date: 2010-10-04, release date: 2010-11-17, Last modification date: 2024-11-20)

Primary citation

Frey, G.,Chen, J.,Rits-Volloch, S.,Freeman, M.M.,Zolla-Pazner, S.,Chen, B.
Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies.
Nat.Struct.Mol.Biol., 17:1486-1491, 2010

PubMed Abstract: HIV-1 envelope glycoprotein gp41 undergoes large conformational changes to drive fusion of viral and target cell membranes, adopting at least three distinct conformations during the viral entry process. Neutralizing antibodies against gp41 block HIV-1 infection by targeting gp41's membrane-proximal external region in a fusion-intermediate state. Here we report biochemical and structural evidence that non-neutralizing antibodies, capable of binding with high affinity to an immunodominant segment adjacent to the neutralizing epitopes in the membrane-proximal region, recognize a gp41 conformation that exists only when membrane fusion is complete. We propose that these non-neutralizing antibodies are induced in HIV-1-infected individuals by gp41 in a triggered, postfusion form and contribute to production of ineffective humoral responses. These results have important implications for gp41-based vaccine design.

PubMed: 21076402
DOI: 10.1038/nsmb.1950

Experimental method

X-RAY DIFFRACTION (3.3 Å)