4jdv

Crystal structure of germ-line precursor of NIH45-46 Fab

spinqualitylabelsall models 4jdv, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jdv 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. Method: X-ray diffraction, Resolution 1.65Å Ligands: 144, 1PE, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Efforts to design an effective antibody-based vaccine against HIV-1 would benefit from understanding how germ-line B-cell receptors (BCRs) recognize the HIV-1 gp120/gp41 envelope spike. Potent VRC01-like (PVL) HIV-1 antibodies derived from the VH1-2*02 germ-line allele target the conserved CD4 binding site on gp120. A bottleneck for design of immunogens capable of eliciting PVL antibodies is that VH1-2*02 germ-line BCR interactions with gp120 are uncharacterized. Here, we report the structure of a VH1-2*02 germ-line antibody alone and a germ-line heavy-chain/mature light-chain chimeric antibody complexed with HIV-1 gp120. VH1-2*02 residues make extensive contacts with the gp120 outer domain, including all PVL signature and CD4 mimicry interactions, but not critical CDRH3 contacts with the gp120 inner domain and bridging sheet that are responsible for the improved potency of NIH45-46 over closely related clonal variants, such as VRC01. Our results provide insight into initial recognition of HIV-1 by VH1-2*02 germ-line BCRs and may facilitate the design of immunogens tailored to engage and stimulate broad and potent CD4 binding site antibodies. Structural basis for HIV-1 gp120 recognition by a germ-line version of a broadly neutralizing antibody.,Scharf L, West AP Jr, Gao H, Lee T, Scheid JF, Nussenzweig MC, Bjorkman PJ, Diskin R Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6049-54. doi:, 10.1073/pnas.1303682110. Epub 2013 Mar 22. PMID:23524883 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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