ملخص
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.
اللغة الأصلية | English |
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الصفحات (من إلى) | 1248-1257 |
عدد الصفحات | 10 |
دورية | European Journal of Immunology |
مستوى الصوت | 45 |
رقم الإصدار | 4 |
المعرِّفات الرقمية للأشياء | |
حالة النشر | Published - أبريل 1 2015 |
ASJC Scopus subject areas
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