7RFC

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

7RFC の概要

• エントリーDOI: 10.2210/pdb7rfc/pdb
• 分子名称: mAb1382 Heavy Chain, mAb1382 Light Chain, envelope glycoprotein E2, ... (7 entities in total)
• 機能のキーワード: hcv glycoprotein, broadly neutralizing antibodies, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 160874.76

構造登録者

Flyak, A.I.,Bjorkman, P.J. (登録日: 2021-07-14, 公開日: 2022-01-12, 最終更新日: 2024-10-09)

主引用文献

Weber, T.,Potthoff, J.,Bizu, S.,Labuhn, M.,Dold, L.,Schoofs, T.,Horning, M.,Ercanoglu, M.S.,Kreer, C.,Gieselmann, L.,Vanshylla, K.,Langhans, B.,Janicki, H.,Stroh, L.J.,Knops, E.,Nierhoff, D.,Spengler, U.,Kaiser, R.,Bjorkman, P.J.,Krey, T.,Bankwitz, D.,Pfeifer, N.,Pietschmann, T.,Flyak, A.I.,Klein, F.
Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.
Immunity, 55:341-354.e7, 2022

PubMed Abstract: 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.

PubMed: 34990590
DOI: 10.1016/j.immuni.2021.12.003

実験手法

X-RAY DIFFRACTION (3.24 Å)