The University of Southampton
University of Southampton Institutional Repository

Tapasin dependence of major histocompatibility complex class I molecules correlates with their conformational flexibility

Garstka, Malgorzata Anna, Fritzsche, Susanne, Lenart, Izabela, Hein, Zeynep, Jankevicius, Gytis, Boyle, Louise H., Elliott, Tim, Trowsdale, John, Antoniou, Antony N., Zacharias, Martin and Springer, Sebastian (2011) Tapasin dependence of major histocompatibility complex class I molecules correlates with their conformational flexibility The FASEB Journal, 25, (11), pp. 3989-3998. (doi:10.1096/fj.11-190249). (PMID:21836024).

Record type: Article

Abstract

Major histocompatibility complex (MHC) class I molecules present cell internally derived peptides at the plasma membrane for surveillance by cytotoxic T lymphocytes. The surface expression of most class I molecules at least partially depends on the endoplasmic reticulum protein, tapasin, which helps them to bind peptides of the right length and sequence. To determine what makes a class I molecule dependent on support by tapasin, we have conducted in silico molecular dynamics (MD) studies and laboratory experiments to assess the conformational state of tapasin-dependent and -independent class I molecules. We find that in the absence of peptide, the region around the F pocket of the peptide binding groove of the tapasin-dependent molecule HLA-B*44:02 is in a disordered conformational state and that it is converted to a conformationally stable state by tapasin. This novel chaperone function of tapasin has not been described previously. We demonstrate that the disordered state of class I is caused by the presence of two adjacent acidic residues in the bottom of the F pocket of class I, and we suggest that conformational disorder is a common feature of tapasin-dependent class I molecules, making them essentially unable to bind peptides on their own. MD simulations are a useful tool to predict such conformational disorder of class I molecules.

Full text not available from this repository.

More information

Published date: November 2011
Keywords: peptide binding, quality control, ligand binding, natively unstructured proteins
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 337332
URI: http://eprints.soton.ac.uk/id/eprint/337332
ISSN: 0892-6638
PURE UUID: 942f7de0-7afd-4fec-a159-246941a61588
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 24 Apr 2012 12:53
Last modified: 18 Jul 2017 06:03

Export record

Altmetrics

Contributors

Author: Malgorzata Anna Garstka
Author: Susanne Fritzsche
Author: Izabela Lenart
Author: Zeynep Hein
Author: Gytis Jankevicius
Author: Louise H. Boyle
Author: Tim Elliott ORCID iD
Author: John Trowsdale
Author: Antony N. Antoniou
Author: Martin Zacharias
Author: Sebastian Springer

University divisions

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.

×