5VGE

Crystal structure of HLA-C*07:02 in complex with RYR peptide

Summary for 5VGE

• Entry DOI: 10.2210/pdb5vge/pdb
• Related: 5VGD
• Descriptor: cDNA FLJ54183, highly similar to HLA class I histocompatibility antigen, Cw-7 alpha chain, Beta-2-microglobulin, ARG-TYR-ARG-PRO-GLY-THR-VAL-ALA-LEU, ... (5 entities in total)
• Functional Keywords: human leukocyte antigen major histocompatibility complex antigen presentation, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 3
• Total formula weight: 44764.51

Authors

Mobbs, J.I.,Vivian, J.P.,Gras, S.,Rossjohn, J. (deposition date: 2017-04-11, release date: 2017-06-07, Last modification date: 2024-11-06)

Primary citation

Kaur, G.,Gras, S.,Mobbs, J.I.,Vivian, J.P.,Cortes, A.,Barber, T.,Kuttikkatte, S.B.,Jensen, L.T.,Attfield, K.E.,Dendrou, C.A.,Carrington, M.,McVean, G.,Purcell, A.W.,Rossjohn, J.,Fugger, L.
Structural and regulatory diversity shape HLA-C protein expression levels.
Nat Commun, 8:15924-15924, 2017

PubMed Abstract: Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression.

PubMed: 28649982
DOI: 10.1038/ncomms15924

Experimental method

X-RAY DIFFRACTION (2.6 Å)