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Two polymorphisms facilitate differences in plasticity between two chicken major histocompatibility complex class I proteins

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Major histocompatibility complex class I molecules (MHC I) present peptides to cytotoxic T-cells at the surface of almost all nucleated cells. The function of MHC I molecules is to select high affinity peptides from a large intracellular pool and they are assisted in this process by co-factor molecules, notably tapasin. In contrast to mammals, MHC homozygous chickens express a single MHC I gene locus, termed BF2, which is hypothesised to have co-evolved with the highly polymorphic tapasin within stable haplotypes. The BF2 molecules of the B15 and B19 haplotypes have recently been shown to differ in their interactions with tapasin and in their peptide selection properties. This study investigated whether these observations might be explained by differences in the protein plasticity that is encoded into the MHC I structure by primary sequence polymorphisms. Furthermore, we aimed to demonstrate the utility of a complimentary modelling approach to the understanding of complex experimental data. Combining mechanistic molecular dynamics simulations and the primary sequence based technique of statistical coupling analysis, we show how two of the eight polymorphisms between BF2*15:01 and BF2*19:01 facilitate differences in plasticity. We show that BF2*15:01 is intrinsically more plastic than BF2*19:01, exploring more conformations in the absence of peptide. We identify a protein sector of contiguous residues connecting the membrane bound ?3 domain and the heavy chain peptide binding site. This sector contains two of the eight polymorphic residues. One is residue 22 in the peptide binding domain and the other 220 is in the ?3 domain, a putative tapasin binding site. These observations are in correspondence with the experimentally observed functional differences of these molecules and suggest a mechanism for how modulation of MHC I plasticity by tapasin catalyses peptide selection allosterically.

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Bailey, Alistair, van Hateren, Andy, Elliott, Tim and Werner, Jörn M., Wang, Junwen(ed.) (2014) Two polymorphisms facilitate differences in plasticity between two chicken major histocompatibility complex class I proteins PLoS ONE, 9, (2), e89657-[11pp]. (doi:10.1371/journal.pone.0089657). (PMID:24586943).

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Accepted/In Press date: 21 January 2014
Published date: 20 February 2014
Organisations: Cancer Sciences


Local EPrints ID: 368153
ISSN: 1932-6203
PURE UUID: c332e70a-7140-4c17-8764-f8b8c86420fe
ORCID for Alistair Bailey: ORCID iD
ORCID for Tim Elliott: ORCID iD
ORCID for Jörn M. Werner: ORCID iD

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Date deposited: 19 Aug 2014 10:18
Last modified: 18 Jul 2017 01:50

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Editor: Junwen Wang
Author: Alistair Bailey ORCID iD
Author: Andy van Hateren
Author: Tim Elliott ORCID iD
Author: Jörn M. Werner ORCID iD

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