3KXF

Crystal Structure of SB27 TCR in complex with the 'restriction triad' mutant HLA-B*3508-13mer

3KXF の概要

• エントリーDOI: 10.2210/pdb3kxf/pdb
• 関連するPDBエントリー: 2AK4 3KWW
• 分子名称: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, SB27 T cell receptor alpha chain, ... (7 entities in total)
• 機能のキーワード: mhc, hla, tcr, disulfide bond, host-virus interaction, immune response, membrane, mhc i, transmembrane, immunoglobulin domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P30685; Secreted: P61769; Host nucleus: P03206
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 384872.25

構造登録者

Archbold, J.K.,Tynan, F.E.,Gras, S.,Rossjohn, J. (登録日: 2009-12-03, 公開日: 2010-06-09, 最終更新日: 2024-10-30)

主引用文献

Burrows, S.R.,Chen, Z.,Archbold, J.K.,Tynan, F.E.,Beddoe, T.,Kjer-Nielsen, L.,Miles, J.J.,Khanna, R.,Moss, D.J.,Liu, Y.C.,Gras, S.,Kostenko, L.,Brennan, R.M.,Clements, C.S.,Brooks, A.G.,Purcell, A.W.,McCluskey, J.,Rossjohn, J.
Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability
Proc.Natl.Acad.Sci.USA, 107:10608-10613, 2010

PubMed Abstract: alphabeta T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactions. Nevertheless, different TCRs adopt a roughly conserved docking mode over the pMHC-I, in which three MHC-I residues (65, 69, and 155) are invariably contacted by the TCR in one way or another. Nonetheless, the impact of mutations at these three positions, either individually or together, was not uniformly detrimental to TCR recognition of pHLA-B*0801 or pHLA-B*3508. Moreover, when TCR-pMHC-I recognition was impaired, this could be partially restored by expression of the CD8 coreceptor. The structure of a TCR-pMHC-I complex in which these three (65, 69, and 155) MHC-I positions were all mutated resulted in shifting of the TCR footprint relative to the cognate complex and formation of compensatory interactions. Collectively, our findings reveal the inherent adaptability of the TCR in maintaining peptide recognition while accommodating changes to the central docking site on the pMHC-I.

PubMed: 20483993
DOI: 10.1073/pnas.1004926107

実験手法

X-RAY DIFFRACTION (3.1 Å)