Leukocyte gelatinase B cleavage releases encephalitogens from human myelin basic protein.
Gelatinase B, a marker enzyme for chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis (MS), was found to cleave human myelin basic protein (MBP). Human MBP was digested with gelatinase B from leukocytes. The MBP peptide fragments were separated by RP-HPLC and the gelatinase B cleavage sites established by aminoterminal sequence analysis. Several novel P1-P1' cleavage sites for gelatinase B were found. The positions of the cleavage sites in human MBP were such that at least one peptide coincided with a documented major MBP-autoantigen. This study annotates human MBP as a substrate for human gelatinase B, determines novel P1-P'1 cleavage sites and defines one of the metalloproteinases as a possible link in the pathogenesis of demyelinating diseases such as MS.
Proost
P
P
Rega Institute for Medical Research, University of Leuven, Belgium.
Van Damme
J
J
Opdenakker
G
G
D000595:Amino Acid Sequence; D015415:Biomarkers; D017364:Collagenases / Q000097:blood* / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D020780:Matrix Metalloproteinase 9; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D010446:Peptide Fragments / Q000302:isolation & purification; D013379:Substrate Specificity
D015415:Biomarkers; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D017364:Collagenases; D020780:Matrix Metalloproteinase 9