Publication date: November 2013 Source:Human Immunology, Volume 74, Supplement
Author(s): Andreas Ziegler , Monika Beerbaum , Martin Ballaschk , Natalja Erdmann , Christina Schnick , Anne Diehl , Barbara Uchanska-Ziegler , Peter Schmieder
Aim ?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 complexes as shown by X-ray crystallography, ?2m is often considered as a mere scaffolding protein. 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. Methods We employ High-Cell-Density Fermentation (HCDF) to obtain deuterated ?2m and Nuclear Magnetic Resonance (NMR) spectroscopy to examine the ?2m-HC interface. Results Following complexation of ?2m, the HLA-B*27:09 HC, and a peptide, the NMR resonance assignments are used to examine the ?2m-HC interface. We then 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 three self-peptides (TIS, pVIPR, pGR) and a viral peptide (pLMP2) for which structural information is already available. The resonance of ?2m-Trp95 does not show any variation in chemical shift, thus serving as an ideal internal control. However, there are distinct resonance signals for ?2m-Trp60 in each of the complexes. Conclusions As these signals are not only distinguishable for a given HLA-B27 subtype, but are also in characteristic positions within the spectra for each of the four peptides employed here, this indicates the existence of an unexpected plasticity that enables ?2m to accommodate changes depending on HC polymorphism as well as on the bound peptide through subtle structural variations of the protein-protein interface.
[NMR paper] NMR spectroscopy reveals unexpected structural variation at the protein-protein interface in MHC class I molecules.
NMR spectroscopy reveals unexpected structural variation at the protein-protein interface in MHC class I molecules.
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...
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Authors: Anderson KM, Esadze A, Manoharan M, Bruschweiler R, Gorenstein DG, Iwahara J
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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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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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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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30-or nmr spectroscopy reveals unexpected structural variation at the protein-protein interface in mhc class i molecules
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