A conserved hydrophobic patch on Vβ domains revealed by TCRβ chain crystal structures: Implications for pre-TCR dimerization.

Frontiers in Immunology
Bo ZhouJia-Huai Wang

Abstract

The αβ T cell receptor (TCR) is a multimeric complex whose β chain plays a crucial role in thymocyte development as well as antigen recognition by mature T lymphocytes. We report here crystal structures of individual β subunits, termed N15β (Vβ5.2Dβ2Jβ2.6Cβ2) and N30β (Vβ13Dβ1Jβ1.1Cβ2), derived from two αβ 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 N15β structure reveals a homodimer formed through two Vβ domains. The Vβ/Vβ module is topologically very similar to the Vα/Vβ module in the N15αβ heterodimer. By contrast, in the N30β structure, the Vβ domain's external hydrophobic CFG face is covered by the neighboring molecule's Cβ 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 Vβ 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 di...Continue Reading

Citations

Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Dibyendu Kumar DasMatthew J Lang
Jun 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Robert J MallisEllis L Reinherz
Jul 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Xinbo Yang, Roy A Mariuzza
Oct 11, 2012·Immunological Reviews·Michael S Kuhns, Hemant B Badgandi
Sep 22, 2015·Frontiers in Immunology·Kristine N BrazinEllis L Reinherz
Feb 25, 2015·Frontiers in Immunology·Hendrik ZieglerKarin Schilbach
Nov 22, 2016·Nature Immunology·Joshua A ViethDerek B Sant'Angelo
Jul 4, 2017·Cellular & Molecular Immunology·Joshua A Vieth, Derek B Sant'Angelo
Aug 16, 2015·Biomolecular NMR Assignments·Robert J MallisHaribabu Arthanari
Jul 16, 2021·Trends in Immunology·Avik DuttaPaul E Love

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BETA
glycosylation

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CNS
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refmac5
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