3O6F

Crystal structure of a human autoimmune TCR MS2-3C8 bound to MHC class II self-ligand MBP/HLA-DR4

3O6F の概要

• エントリーDOI: 10.2210/pdb3o6f/pdb
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-4 beta chain, T-cell receptor alpha chain C region, ... (5 entities in total)
• 機能のキーワード: autoimmunity, multiple sclerosis, t cell receptor, hla class ii, protein-protein complex, immunoglobulin fold, membrane, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P01903 P13760; Membrane ; Single-pass membrane protein : P01848 A0A5B9
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 193200.94

構造登録者

Yin, Y.,Li, Y.,Martin, R.,Mariuzza, R.A. (登録日: 2010-07-29, 公開日: 2011-03-02, 最終更新日: 2024-11-20)

主引用文献

Yin, Y.,Li, Y.,Kerzic, M.C.,Martin, R.,Mariuzza, R.A.
Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection.
Embo J., 30:1137-1148, 2011

PubMed Abstract: The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3β conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity.

PubMed: 21297580
DOI: 10.1038/emboj.2011.21

実験手法

X-RAY DIFFRACTION (2.8 Å)