F pocket flexibility influences the tapasin dependence of two differentially disease‐associated MHC Class I proteins. Issue 4 (14th February 2015)

• Record Type: Journal Article
• Authors: Abualrous, Esam T.; Fritzsche, Susanne; Hein, Zeynep; Al‐Balushi, Mohammed S.; Reinink, Peter; Boyle, Louise H.; Wellbrock, Ursula; Antoniou, Antony N.; Springer, Sebastian
• Is Part Of: European journal of immunology. Volume 45:Issue 4(2015:Apr.)
• Page Start: 1248
• Page End: 1257
• Publication Date: 2015-02-14
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201445307
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> <p>Also watch the <ext-link ext-link-type="uri" xlink:href="https://www.youtube.com/watch?v=F7UKhYqU79A" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">Video Abstract</ext-link></p> </abstract>