3OF6

Human pre-T cell receptor crystal structure

3OF6 の概要

• エントリーDOI: 10.2210/pdb3of6/pdb
• 関連するPDBエントリー: 1KGC
• 分子名称: T cell receptor beta chain, Pre T-cell antigen receptor alpha, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: ig fold, 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 (Potential): Q6ISU1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 126871.24

構造登録者

Pang, S.S. (登録日: 2010-08-13, 公開日: 2010-10-20, 最終更新日: 2024-10-30)

主引用文献

Pang, S.S.,Berry, R.,Chen, Z.,Kjer-Nielsen, L.,Perugini, M.A.,King, G.F.,Wang, C.,Chew, S.H.,La Gruta, N.L.,Williams, N.K.,Beddoe, T.,Tiganis, T.,Cowieson, N.P.,Godfrey, D.I.,Purcell, A.W.,Wilce, M.C.J.,McCluskey, J.,Rossjohn, J.
The structural basis for autonomous dimerization of the pre-T-cell antigen receptor
Nature, 467:844-848, 2010

PubMed Abstract: The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR β-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent αβ T-cell lineage differentiation. Whereas αβTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant α-chain (pre-Tα) that pairs with any TCR β-chain (TCRβ) following successful TCR β-gene rearrangement. Here we provide the basis of pre-Tα-TCRβ assembly and pre-TCR dimerization. The pre-Tα chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR α-chain; nevertheless, the mode of association between pre-Tα and TCRβ mirrored that mediated by the Cα-Cβ domains of the αβTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Tα domain to interact with the variable (V) β domain through residues that are highly conserved across the Vβ and joining (J) β gene families, thus mimicking the interactions at the core of the αβTCR's Vα-Vβ interface. Disruption of this pre-Tα-Vβ dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Tα chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR β-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Tα represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.

PubMed: 20944746
DOI: 10.1038/nature09448

実験手法

X-RAY DIFFRACTION (2.8 Å)