The University of Southampton
University of Southampton Institutional Repository

Dual conformations of a T cell receptor Vα homodimer: Implications for variability in VαVβ domain association

Dual conformations of a T cell receptor Vα homodimer: Implications for variability in VαVβ domain association
Dual conformations of a T cell receptor Vα homodimer: Implications for variability in VαVβ domain association

The crystal structure of a mutant T cell receptor (TCR) Vα domain containing a grafted third complementarity-determining region (CDR3) from a different Vα was determined at 2.3 Å resolution by molecular replacement using the wild-type Vα structure as a search model. Like the wild-type Vα domain, the mutant crystallized as a homodimer very similar to TCR VαVβ and antibody V(L)V(H) heterodimers, with the CDR loops disposed to form part of the antigen-binding site. However, the relative orientation of the two chains in the mutant Vα homodimer differs from that in the wild-type by a rotation of 14°such that the buried surface area in the dimer interface of the mutant is 140 Å2 less than in the wild-type. While the residues forming the interface are essentially the same in the two structures, there are only four pairs of interface hydrogen bonds in the case of the mutant compared with eight for the wild-type. These results suggest that multiple relative orientations of the Vα and Vβ domains of TCRs may be possible, providing a significant contribution to TCR combining site diversity.

Site-directed mutagenesis, T cell receptor, Three-dimensional structure, V domain association, Vα domain
0022-2836
385-394
Li, Hongmin
ac67738d-fcdf-49e2-aff9-515f415ccf35
Lebedeva, Marina I.
b150ad1a-0c37-4bb9-b908-79e95ba08744
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Mariuzza, Roy A.
e81103c5-af20-4034-8d29-0c24b2a98b40
Li, Hongmin
ac67738d-fcdf-49e2-aff9-515f415ccf35
Lebedeva, Marina I.
b150ad1a-0c37-4bb9-b908-79e95ba08744
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Mariuzza, Roy A.
e81103c5-af20-4034-8d29-0c24b2a98b40

Li, Hongmin, Lebedeva, Marina I., Ward, E. Sally and Mariuzza, Roy A. (1997) Dual conformations of a T cell receptor Vα homodimer: Implications for variability in VαVβ domain association. Journal of Molecular Biology, 269 (3), 385-394. (doi:10.1006/jmbi.1997.1047).

Record type: Article

Abstract

The crystal structure of a mutant T cell receptor (TCR) Vα domain containing a grafted third complementarity-determining region (CDR3) from a different Vα was determined at 2.3 Å resolution by molecular replacement using the wild-type Vα structure as a search model. Like the wild-type Vα domain, the mutant crystallized as a homodimer very similar to TCR VαVβ and antibody V(L)V(H) heterodimers, with the CDR loops disposed to form part of the antigen-binding site. However, the relative orientation of the two chains in the mutant Vα homodimer differs from that in the wild-type by a rotation of 14°such that the buried surface area in the dimer interface of the mutant is 140 Å2 less than in the wild-type. While the residues forming the interface are essentially the same in the two structures, there are only four pairs of interface hydrogen bonds in the case of the mutant compared with eight for the wild-type. These results suggest that multiple relative orientations of the Vα and Vβ domains of TCRs may be possible, providing a significant contribution to TCR combining site diversity.

This record has no associated files available for download.

More information

Accepted/In Press date: 13 March 1997
Published date: 13 June 1997
Keywords: Site-directed mutagenesis, T cell receptor, Three-dimensional structure, V domain association, Vα domain

Identifiers

Local EPrints ID: 425121
URI: http://eprints.soton.ac.uk/id/eprint/425121
ISSN: 0022-2836
PURE UUID: eabbc1a8-cc50-40d0-9fcc-d3fb9776c8eb
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 11 Oct 2018 16:30
Last modified: 18 Mar 2024 03:48

Export record

Altmetrics

Contributors

Author: Hongmin Li
Author: Marina I. Lebedeva
Author: E. Sally Ward ORCID iD
Author: Roy A. Mariuzza

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×