An Alternative Conformation of the T-Cell Receptor a Constant Region

JOURNAL OF MOLECULAR BIOLOGY

卷:400

Article

van Boxel, Gijs I.²  Holmes, Samantha²  Fugger, Lars^1,3  Jones, E. Yvonne² 

[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DS, England

[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England

[3] Aarhus Univ Hosp, Dept Clin Immunol, DK-8000 Aarhus N, Denmark

关键词: T-cell receptor;    conformational change;    crystal structure;    signaling;    metamorphic proteins;   

DOI  :  10.1016/j.jmb.2010.05.053

来源: Elsevier

【 摘 要 】

alpha beta T-cell receptors (TcRs) play a central role in cellular immune response. They are members of the Ig superfamily, with extracellular regions of the a and p chains each comprising a V-type domain and a C-type domain. We have determined the ectodomain structure of an alpha beta TcR, which recognizes the autoantigen myelin basic protein. The 2.0-angstrom-resolution structure reveals canonical main-chain conformations for the V-alpha, V-beta, and C-beta domains, but the C-alpha domain exhibits a main-chain conformation remarkably different from those previously reported for TcR crystal structures. The global IgC-like fold is maintained, but a piston-like rearrangement between BC and DE beta-turns results in beta-strand slippage. This substantial conformational change may represent a signaling intermediate. Our structure is the first example for the Ig fold of the increasingly recognized concept of metamorphic proteins. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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