Title |
NMR spectroscopy reveals unexpected structural variation at the protein–protein interface in MHC class I molecules
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Published in |
Journal of Biomolecular NMR, September 2013
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DOI | 10.1007/s10858-013-9777-z |
Pubmed ID | |
Authors |
Monika Beerbaum, Martin Ballaschk, Natalja Erdmann, Christina Schnick, Anne Diehl, Barbara Uchanska-Ziegler, Andreas Ziegler, Peter Schmieder |
Abstract |
β2-Microglobulin (β2m) is a small, monomorphic protein non-covalently bound to the heavy chain (HC) in polymorphic major histocompatibility complex (MHC) class I molecules. Given the high evolutionary conservation of structural features of β2m in various MHC molecules as shown by X-ray crystallography, β2m is often considered as a mere scaffolding protein. Using nuclear magnetic resonance (NMR) spectroscopy, we investigate here whether β2m residues at the interface to the HC exhibit changes depending on HC polymorphisms and the peptides bound to the complex in solution. First we show that human β2m can effectively be produced in deuterated form using high-cell-density-fermentation and we employ the NMR resonance assignments obtained for triple-labeled β2m bound to the HLA-B*27:09 HC to examine the β2m-HC interface. We then proceed to compare the resonances of β2m in two minimally distinct subtypes, HLA-B*27:09 and HLA-B*27:05, that are differentially associated with the spondyloarthropathy Ankylosing Spondylitis. Each of these subtypes is complexed with four distinct peptides for which structural information is already available. We find that only the resonances at the β2m-HC interface show a variation of their chemical shifts between the different complexes. This indicates the existence of an unexpected plasticity that enables β2m to accommodate changes that depend on HC polymorphism as well as on the bound peptide through subtle structural variations of the protein-protein interface. |
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Student > Master | 5 | 14% |
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Physics and Astronomy | 2 | 6% |
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