TAILIEUCHUNG - Báo cáo khoa học: Solution NMR structure of an immunodominant epitope of myelin basic protein Conformational dependence on environment of an intrinsically unstructured protein

Using solution NMR spectroscopy, three-dimensional structures have been obtained for an 18-residue synthetic polypeptide fragment of kDa myelin basic protein (MBP, human residues Q81–T98) under three condi-tions emulating the protein’s natural environment in the myelin membrane to varying degrees: (a) an aqueous solution (100 mmKCl pH ), (b) a mixture of trifluoroethanol (TFE-d2) and water (30 : 70% v⁄v), and (c) a dispersion of 100 mm dodecylphosphocholine (DPC-d38 , 1 : 100 pro-tein⁄lipid molar ratio) micelles | ềFEBS Journal Solution NMR structure of an immunodominant epitope of myelin basic protein Conformational dependence on environment of an intrinsically unstructured protein Christophe Fares1 David S. Libich1 and George Harauz1 1 Department of Molecular and Cellular Biology and Biophysics InterdepartmentalGroup University of Guelph Canada Keywords correlation spectroscopy multiple sclerosis myelin basic protein immunodominant epitope solution NMR Correspondence G. Harauz Department of Molecular and Cellular Biology and Biophysics InterdepartmentalGroup University of Guelph 50 Stone Road East Guelph Ontario Canada N1G 2W1 Fax 1 519 837 2075 Tel 1 519 824 4120 ext. 52535 E-mail gharauz@ Present address Max-Planck-Institut fur Biophysikalische Chemie NMR-Based StructuralBiology Gottingen Germany. Christophe Fares and David S. Libich contributed equally to this work. Received 19 October 2005 revised 1 December 2005 accepted 7 December 2005 Using solution NMR spectroscopy three-dimensional structures have been obtained for an 18-residue synthetic polypeptide fragment of 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 mM KCl pH b a mixture of trifluoroethanol TFE-d2 and water 30 70 v v and c a dispersion of 100 mM dodecylphosphocholine DPC-d38 1 100 pro-tein 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 a 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 a helix in .

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