4HK3

I2 Fab (unbound) from CH65-CH67 Lineage

4HK3 の概要

• エントリーDOI: 10.2210/pdb4hk3/pdb
• 関連するPDBエントリー: 4HK0 4HKB 4HKX
• 分子名称: I2 heavy chain, I2 light chain (2 entities in total)
• 機能のキーワード: fab fragment, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48467.77

構造登録者

Schmidt, A.G.,Harrison, S.C. (登録日: 2012-10-14, 公開日: 2012-11-21, 最終更新日: 2024-11-20)

主引用文献

Schmidt, A.G.,Xu, H.,Khan, A.R.,O'Donnell, T.,Khurana, S.,King, L.R.,Manischewitz, J.,Golding, H.,Suphaphiphat, P.,Carfi, A.,Settembre, E.C.,Dormitzer, P.R.,Kepler, T.B.,Zhang, R.,Moody, M.A.,Haynes, B.F.,Liao, H.X.,Shaw, D.E.,Harrison, S.C.
Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.
Proc.Natl.Acad.Sci.USA, 110:264-269, 2013

PubMed Abstract: Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines.

PubMed: 23175789
DOI: 10.1073/pnas.1218256109

実験手法

X-RAY DIFFRACTION (3 Å)