6MEF

Crystal structure of broadly neutralizing antibody AR3C

6MEF の概要

• エントリーDOI: 10.2210/pdb6mef/pdb
• 関連するPDBエントリー: 6MED 6MEE 6MEG 6MEH 6MEI 6MEJ 6MEK
• 分子名称: antibody AR3C Heavy Chain, antibody AR3C Light Chain (2 entities in total)
• 機能のキーワード: hcv glycoprotein, broadly neutralizing antibodies, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48838.30

構造登録者

Flyak, A.I.,Bjorkman, P.J. (登録日: 2018-09-06, 公開日: 2018-11-21, 最終更新日: 2024-11-13)

主引用文献

Flyak, A.I.,Ruiz, S.,Colbert, M.D.,Luong, T.,Crowe Jr., J.E.,Bailey, J.R.,Bjorkman, P.J.
HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design.
Cell Host Microbe, 24:703-716.e3, 2018

PubMed Abstract: Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations. The structures display unusual features relevant to common genetic signatures of HCV bNAbs and demonstrate extraordinary plasticity in antibody-antigen interactions. In addition, E2 variants that bind HEPC3/HEPC74-like germline precursors may represent candidate vaccine immunogens.

PubMed: 30439340
DOI: 10.1016/j.chom.2018.10.009

実験手法

X-RAY DIFFRACTION (2.9 Å)