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A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization

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...

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Autores principales: Zhou, Bo, Chen, Qiang, Mallis, Robert J., Zhang, Hongmin, Liu, Jin-huan, Reinherz, Ellis L., Wang, Jia-huai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341985/
https://www.ncbi.nlm.nih.gov/pubmed/22566796
http://dx.doi.org/10.3389/fimmu.2011.00005
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author Zhou, Bo
Chen, Qiang
Mallis, Robert J.
Zhang, Hongmin
Liu, Jin-huan
Reinherz, Ellis L.
Wang, Jia-huai
author_facet Zhou, Bo
Chen, Qiang
Mallis, Robert J.
Zhang, Hongmin
Liu, Jin-huan
Reinherz, Ellis L.
Wang, Jia-huai
author_sort Zhou, Bo
collection PubMed
description 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 distinct from those suggested previously by others and discuss its functional and structural implications.
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spelling pubmed-33419852012-05-07 A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization Zhou, Bo Chen, Qiang Mallis, Robert J. Zhang, Hongmin Liu, Jin-huan Reinherz, Ellis L. Wang, Jia-huai Front Immunol Immunology 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 distinct from those suggested previously by others and discuss its functional and structural implications. Frontiers Research Foundation 2011-03-01 /pmc/articles/PMC3341985/ /pubmed/22566796 http://dx.doi.org/10.3389/fimmu.2011.00005 Text en Copyright © 2011 Zhou, Chen, Mallis, Zhang, Liu, Reinherz and Wang. http://www.frontiersin.org/licenseagreement This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
spellingShingle Immunology
Zhou, Bo
Chen, Qiang
Mallis, Robert J.
Zhang, Hongmin
Liu, Jin-huan
Reinherz, Ellis L.
Wang, Jia-huai
A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization
title A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization
title_full A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization
title_fullStr A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization
title_full_unstemmed A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization
title_short A Conserved Hydrophobic Patch on Vβ Domains Revealed by TCRβ Chain Crystal Structures: Implications for Pre-TCR Dimerization
title_sort conserved hydrophobic patch on vβ domains revealed by tcrβ chain crystal structures: implications for pre-tcr dimerization
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341985/
https://www.ncbi.nlm.nih.gov/pubmed/22566796
http://dx.doi.org/10.3389/fimmu.2011.00005
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