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

Esam T. Abualrous, Susanne Fritzsche, Zeynep Hein, Mohammed S. Al-Balushi, Peter Reinink, Louise H. Boyle, Ursula Wellbrock, Antony N. Antoniou, Sebastian Springer*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1248-1257
Number of pages10
JournalEuropean Journal of Immunology
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • Ankylosing spondylitis
  • HLA-B27
  • Major histocompatibility complex
  • Molecular dynamics
  • Natively unstructured proteins
  • Protein folding
  • Simulations

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Fingerprint Dive into the research topics of 'F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins'. Together they form a unique fingerprint.

  • Cite this

    Abualrous, E. T., Fritzsche, S., Hein, Z., Al-Balushi, M. S., Reinink, P., Boyle, L. H., Wellbrock, U., Antoniou, A. N., & Springer, S. (2015). F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins. European Journal of Immunology, 45(4), 1248-1257. https://doi.org/10.1002/eji.201445307