NMR spectroscopy reveals unexpected structural variation at the protein-protein interface in MHC class I molecules.
J Biomol NMR. 2013 Sep 5;
Authors: Beerbaum M, Ballaschk M, Erdmann N, Schnick C, Diehl A, Uchanska-Ziegler B, Ziegler A, Schmieder P
Abstract
?2-Microglobulin (?2m) 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 ?2m in various MHC molecules as shown by X-ray crystallography, ?2m is often considered as a mere scaffolding protein. Using nuclear magnetic resonance (NMR) spectroscopy, we investigate here whether ?2m 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 ?2m can effectively be produced in deuterated form using high-cell-density-fermentation and we employ the NMR resonance assignments obtained for triple-labeled ?2m bound to the HLA-B*27:09 HC to examine the ?2m-HC interface. We then proceed to compare the resonances of ?2m 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 ?2m-HC interface show a variation of their chemical shifts between the different complexes. This indicates the existence of an unexpected plasticity that enables ?2m to accommodate changes that depend on HC polymorphism as well as on the bound peptide through subtle structural variations of the protein-protein interface.
PMID: 24006098 [PubMed - as supplied by publisher]
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J Am Chem Soc. 2013 Feb 14;
Authors: Anderson KM, Esadze A, Manoharan M, Bruschweiler R, Gorenstein DG, Iwahara J
Abstract
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02-15-2013 05:21 PM
1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems
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Abstract The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological...
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03-03-2011 02:06 AM
Small molecules against Ebola: NMR reveals drug leads
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There is neither vaccine nor cure for the Ebola virus, which causes fatal haemorrhagic fever in humans. However, a new NMR spectroscopic study by US researchers scientists has led to the discovery of a family of small molecules that apparently bind to the outer protein coat of the virus and halt its entry into human cells, so offering the possibility of an antiviral medication against the disease.
Source: Spectroscopynow.com
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Authors: Miura T, Klaus W, Gsell B, Miyamoto C, Senn H
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Solid-State NMR Reveals Structural and Dynamical Properties of a Membrane Protein
http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/2007/129/i21/abs/ja069028m.html
Solid-State NMR Reveals Structural and Dynamical Properties of a Membrane-Anchored Electron-Carrier Protein, Cytochrome b<sub>5</sub>
<aui auinm="Durr, U. H. N."> <aui auinm="Yamamoto, K."> <aui auinm="Im, S.-C."> <aui auinm="Waskell, L."> <aui auinm="Ramamoorthy, A."> <aug><aul></aul></aug></aui></aui></aui></aui></aui> <au>Ulrich H. N. Dürr,</au> <au>Kazutoshi Yamamoto,</au><au>Sang-Choul Im,</au><au>Lucy Waskell,and </au><au>Ayyalusamy Ramamoorthy*</au>
*ramamoor@umich.edu
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