A Conserved Hydrophobic Patch on V\(\beta\) Domains Revealed by TCR\(\beta\) Chain Crystal Structures: Implications for Pre-TCR Dimerization

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Zhang, Hongmin
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https://doi.org/10.3389/fimmu.2011.00005Metadata
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Zhou, Bo, Qiang Chen, Robert J. Mallis, Hongmin Zhang, Jin-huan Liu, Ellis L. Reinherz, and Jia-huai Wang. 2011. A conserved hydrophobic patch on V\(\beta\) domains revealed by TCR\(\beta\) chain crystal structures: Implications for pre-TCR dimerization. Frontiers in Immunology 2:5.Abstract
The \(\alpha\beta\) T cell receptor (TCR) is a multimeric complex whose \(\beta\) chain plays a crucial role in thymocyte development as well as antigen recognition by mature T lymphocytes. We report here crystal structures of individual \(\beta\) subunits, termed N15\(\beta\) (V\(\beta\)5.2D\(\beta\)2J\(\beta\)2.6C\(\beta\)2) and N30\(\beta\) (V\(\beta\)13D\(\beta\)1J\(\beta\)1.1C\(\beta\)2), derived from two \(\alpha\beta\) TCRs specific for the immunodominant vesicular stomatitis virus octapeptide (VSV-8) bound to the murine H-2K\(^b\) MHC class I molecule. The crystal packing of the N15\(\beta\) structure reveals a homodimer formed through two V\(\beta\) domains. The V\(\beta\)/V\(\beta\) module is topologically very similar to the V\(\alpha\)/V\(\beta\) module in the N15\(\alpha\beta\) heterodimer. By contrast, in the N30\(\beta\) structure, the V\(\beta\) domain’s external hydrophobic CFG face is covered by the neighboring molecule’s C\(\beta\) domain. In conjunction with systematic investigation of previously published TCR single-subunit structures, we identified several conserved residues forming a concave hydrophobic patch at the center of the CFG outer face of the V\(\beta\) and other V-type Ig-like domains. This hydrophobic patch is shielded from solvent exposure in the crystal packing, implying that it is unlikely to be thermodynamically stable if exposed on the thymocyte surface. Accordingly, we propose a dimeric pre-TCR model distinct from those suggested previously by others and discuss its functional and structural implications.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341985/pdf/Terms of Use
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