7rfc

Crystal structure of broadly neutralizing antibody mAb1382 in complex with Hepatitis C virus envelope glycoprotein E2 ectodomain

spinqualitylabelsall models 7rfc, resolution 3.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rfc is a 6 chain structure with sequence from Hepacivirus hominis and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.24Å Ligands: BMA, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy-chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates. Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.,Weber T, Potthoff J, Bizu S, Labuhn M, Dold L, Schoofs T, Horning M, Ercanoglu MS, Kreer C, Gieselmann L, Vanshylla K, Langhans B, Janicki H, Stroh LJ, Knops E, Nierhoff D, Spengler U, Kaiser R, Bjorkman PJ, Krey T, Bankwitz D, Pfeifer N, Pietschmann T, Flyak AI, Klein F Immunity. 2022 Feb 8;55(2):341-354.e7. doi: 10.1016/j.immuni.2021.12.003. Epub , 2022 Jan 5. PMID:34990590 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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