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Solution NMR structure of an immunodominant epitope of myelin basic protein
Author(s) -
Farès Christophe,
Libich David S.,
Harauz George
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.05093.x
Subject(s) - epitope , chemistry , myelin basic protein , aqueous solution , heteronuclear molecule , helix (gastropod) , nuclear magnetic resonance spectroscopy , linear epitope , micelle , protein structure , protein secondary structure , crystallography , myelin , biophysics , peptide sequence , stereochemistry , biochemistry , antibody , biology , organic chemistry , gene , ecology , neuroscience , snail , immunology , central nervous system
Using solution NMR spectroscopy, three‐dimensional structures have been obtained for an 18‐residue synthetic polypeptide fragment of 18.5 kDa myelin basic protein (MBP, human residues Q81–T98) under three conditions emulating the protein's natural environment in the myelin membrane to varying degrees: (a) an aqueous solution (100 m m KCl pH 6.5), (b) a mixture of trifluoroethanol (TFE‐d 2 ) and water (30 : 70% v/v), and (c) a dispersion of 100 m m dodecylphosphocholine (DPC‐d 38 , 1 : 100 protein/lipid molar ratio) micelles. This polypeptide sequence is highly conserved in MBP from mammals, amphibians, and birds, and comprises a major immunodominant epitope (human residues N83–T92) in the autoimmune disease multiple sclerosis. In the polypeptide fragment, this epitope forms a stable, amphipathic, α helix under organic and membrane‐mimetic conditions, but has only a partially helical conformation in aqueous solution. These results are consistent with recent molecular dynamics simulations that showed this segment to have a propensity to form a transient α helix in aqueous solution, and with electron paramagnetic resonance (EPR) experiments that suggested a α‐helical structure when bound to a membrane [I. R. Bates, J. B. Feix, J. M. Boggs & G. Harauz (2004) J Biol Chem , 279 , 5757–5764]. The high sensitivity of the epitope structure to its environment is characteristic of intrinsically unstructured proteins, like MBP, and reflects its association with diverse ligands such as lipids and other proteins.