F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins

Abualrous, Esam, Fritzsche, Susanne, Hein, Zeynep, Al-Balushi, Mohammed, Reinink, Peter, Boyle, Louise, Wellbrock, Ursula, Antoniou, Antony and Springer, Sebastian (2015) F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins. European Journal of Immunology, 45 (4). pp. 1248-1257. ISSN 0014-2980

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Abstract

The human MHC class I protein HLA‐B*27:05 is statistically associated with ankylosing spondylitis, unlike HLA‐B*27:09, which differs in a single amino acid in the F pocket of the peptide‐binding groove. To understand how this unique amino acid difference leads to a different behavior of the proteins in the cell, we have investigated the conformational stability of both proteins using a combination of in silico and experimental approaches. Here, we show that the binding site of B*27:05 is conformationally disordered in the absence of peptide due to a charge repulsion at the bottom of the F pocket. In agreement with this, B*27:05 requires the chaperone protein tapasin to a greater extent than the conformationally stable B*27:09 in order to remain structured and to bind peptide. Taken together, our data demonstrate a method to predict tapasin dependence and physiological behavior from the sequence and crystal structure of a particular class I allotype.

Item Type:	Article
Subjects:	C900 Others in Biological Sciences
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Becky Skoyles
Date Deposited:	10 Aug 2018 14:49
Last Modified:	11 Oct 2019 19:45
URI:	http://nrl.northumbria.ac.uk/id/eprint/35272

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