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.

spinqualitylabelsall models 4nhc, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nhc is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.912Å Ligands: ACE, DIV, MK8, PO4, PRD_001209, TFA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Hydrocarbon stapling can restore bioactive alpha-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 alpha-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. Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies.,Bird GH, Irimia A, Ofek G, Kwong PD, Wilson IA, Walensky LD Nat Struct Mol Biol. 2014 Nov 24. doi: 10.1038/nsmb.2922. PMID:25420104 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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