title: Isoaspartic acid is present at specific sites in myelin basic protein from multiple sclerosis patients: could this represent a trigger for disease onset?
abstract: Multiple sclerosis (MS) is associated with breakdown of the myelin sheath that coats neurons in the central nervous system. The cause of MS is not known, although the pathogenesis involves destruction of myelin by the immune system. It was the aim of this study to examine the abundant myelin protein, myelin basic protein (MBP), to determine if there are sites of modification that may be characteristic for MS. MBP from the cerebellum was examined from controls and MS patients across the age range using mass spectrometry and amino acid analysis. Amino acid racemization data indicated that myelin basic protein is long-lived and proteomic analysis of MBP showed it to be highly modified. A common modification of MBP was racemization of Asp and this was significantly greater in MS patients. In long-lived proteins, L-Asp and L-Asn can racemize to three other isomers, D-isoAsp, L-isoAsp and D-Asp and this is significant because isoAsp formation in peptides renders them immunogenic.Proteomic analysis revealed widespread modifications of MBP with two surface regions that are altered in MS. In particular, isoAsp was significantly elevated at these sites in MS patients. The generation of isoAsp could be responsible for eliciting an immune response to modified MBP and therefore be implicated in the etiology of MS.
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.|School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia.
authors: Michael G
authors: MG
authors: Friedrich
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.|School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia.
authors: Sarah E
authors: SE
authors: Hancock
authors: Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, 2052, Australia.
authors: Mark J
authors: MJ
authors: Raftery
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia. rjwt@uow.edu.au.
authors: Roger J W
authors: RJ
authors: Truscott
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D026581:Isoaspartic Acid / Q000378:metabolism*; D013058:Mass Spectrometry; D008875:Middle Aged; D008958:Models, Molecular; D020528:Multiple Sclerosis, Chronic Progressive / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis
chemical_list: D026581:Isoaspartic Acid; C499048:MBP protein, human; D004676:Myelin Basic Protein; D005973:Glutamine; D001224:Aspartic Acid; D001120:Arginine