4N1C

Structural evidence for antigen receptor evolution

4N1C の概要

• エントリーDOI: 10.2210/pdb4n1c/pdb
• 関連するPDBエントリー: 4N1E
• 分子名称: immunoglobulin variable light chain domain, Lysozyme C (3 entities in total)
• 機能のキーワード: immunoglobulin variable domain homodimer, protein-protein complex, ig domain, immune system-hydrolase complex, immune system/hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P00698
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 38279.72

構造登録者

Langley, D.B.,Rouet, R.,Roome, B.,Stock, D.,Christ, D. (登録日: 2013-10-03, 公開日: 2014-10-29, 最終更新日: 2024-10-09)

主引用文献

Rouet, R.,Langley, D.B.,Schofield, P.,Christie, M.,Roome, B.,Porebski, B.T.,Buckle, A.M.,Clifton, B.E.,Jackson, C.J.,Stock, D.,Christ, D.
Structural reconstruction of protein ancestry.
Proc. Natl. Acad. Sci. U.S.A., 114:3897-3902, 2017

PubMed Abstract: Ancestral protein reconstruction allows the resurrection and characterization of ancient proteins based on computational analyses of sequences of modern-day proteins. Unfortunately, many protein families are highly divergent and not suitable for sequence-based reconstruction approaches. This limitation is exemplified by the antigen receptors of jawed vertebrates (B- and T-cell receptors), heterodimers formed by pairs of Ig domains. These receptors are believed to have evolved from an extinct homodimeric ancestor through a process of gene duplication and diversification; however molecular evidence has so far remained elusive. Here, we use a structural approach and laboratory evolution to reconstruct such molecules and characterize their interaction with antigen. High-resolution crystal structures of reconstructed homodimeric receptors in complex with hen-egg white lysozyme demonstrate how nanomolar affinity binding of asymmetrical antigen is enabled through selective recruitment and structural plasticity within the receptor-binding site. Our results provide structural evidence in support of long-held theories concerning the evolution of antigen receptors, and provide a blueprint for the experimental reconstruction of protein ancestry in the absence of phylogenetic evidence.

PubMed: 28356519
DOI: 10.1073/pnas.1613477114

実験手法

X-RAY DIFFRACTION (1.7 Å)