4NHC

Crystal structure of the HIV-1 neutralizing antibody 4E10 Fab fragment in complex with a hydrocarbon-stapled peptide containing the 4e10 epitope on gp41.

Summary for 4NHC

• Entry DOI: 10.2210/pdb4nhc/pdb
• Related: 4NGH
• Related PRD ID: PRD_001209
• Descriptor: FAB LIGHT CHAIN, FAB HEAVY CHAIN, MODIFIED FRAGMENT OF HIV GLYCOPROTEIN (GP41), ... (6 entities in total)
• Functional Keywords: immunoglobulin fold, beta-sandwich, 4e10 fab, antibody-epitope complex, gp41 hiv-1, hydrocarbon staple, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 49798.46

Authors

Irimia, A.,Wilson, I.A. (deposition date: 2013-11-04, release date: 2014-12-03, Last modification date: 2023-12-06)

Primary citation

Bird, G.H.,Irimia, A.,Ofek, G.,Kwong, P.D.,Wilson, I.A.,Walensky, L.D.
Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies.
Nat.Struct.Mol.Biol., 21:1058-1067, 2014

PubMed Abstract: Hydrocarbon stapling can restore bioactive α-helical structure to natural peptides, yielding research tools and prototype therapeutics to dissect and target protein interactions. Here we explore the capacity of peptide stapling to generate high-fidelity, protease-resistant mimics of antigenic structures for vaccine development. HIV-1 has been refractory to vaccine technologies thus far, although select human antibodies can broadly neutralize HIV-1 by targeting sequences of the gp41 juxtamembrane fusion apparatus. To develop candidate HIV-1 immunogens, we generated and characterized stabilized α-helices of the membrane-proximal external region (SAH-MPER) of gp41. SAH-MPER peptides were remarkably protease resistant and bound to the broadly neutralizing 4E10 and 10E8 antibodies with high affinity, recapitulating the structure of the MPER epitope when differentially engaged by the two anti-HIV Fabs. Thus, stapled peptides may provide a new opportunity to develop chemically stabilized antigens for vaccination.

PubMed: 25420104
DOI: 10.1038/nsmb.2922

Experimental method

X-RAY DIFFRACTION (2.912 Å)