Title : The structural basis for autonomous
dimerization of the pre-T-cell antigen
receptor
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 αβ TCR 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 αβ TCR
- 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 αβ TCR '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
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 5. -, domain
- 5. TCR α-, domain
- 5. TCR, domains
- 9. TCR β-chain, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):