4nrz | pdb_00004nrz

Crystal Structure of HIV-1 Neutralizing Antibody m66.6

spinqualitylabelsall models 4nrz, resolution 2.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nrz is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Antibodies m66.6 and 2F5 are the only effective human HIV-1-neutralizing antibodies identified thus far that recognize the N-terminal region of the membrane-proximal external region (MPER) of the gp41 subunit of the HIV-1 viral spike. Although 2F5 has been extensively characterized, much less is known about antibody m66.6 or antibody m66, a closely related light-chain variant. Here, we report the crystal structure of m66 in complex with its gp41 epitope, along with unbound structures of m66 and m66.6. We employed mutational and binding analyses to decipher antibody elements critical for recognition of their gp41 epitopes, and determined the molecular basis that underlies their neutralization of HIV-1. When bound by m66, the N-terminal region of the gp41 MPER adopts a conformation comprising a helix followed by an extended loop. Comparison of gp41-bound m66 with unbound m66.6 identified three light chain residues of m66.6 that were confirmed through mutagenesis to underlie the superior breadth and potency of m66.6-mediated virus neutralization. Recognition of gp41 by m66 also revealed similarities to antibody 2F5 both in the conformation of crucial epitope residues as well as in the angles of antibody approach. Aromatic residues at the tip of the m66.6-heavy chain third complementarity-determining region, as in the case of 2F5, were determined to be critical for virus neutralization in a manner that correlated with antibody recognition of the MPER in a lipid context. Antibodies m66, m66.6, and 2F5 thus utilize similar mechanistic elements to recognize a common gp41-MPER epitope and neutralize HIV-1. Structural Basis for HIV-1 Neutralization by 2F5-like Antibodies m66 and m66.6.,Ofek G, Zirkle B, Yang Y, Zhu Z, McKee K, Zhang B, Chuang GY, Georgiev IS, O'Dell S, Doria-Rose N, Mascola JR, Dimitrov DS, Kwong PD J Virol. 2013 Dec 11. PMID:24335316 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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