Membrane-type 1 MMP (MMP-14) cleaves at three sites in the aggrecan interglobular domain.
An aggrecan G1-G2 substrate was used to determine sites within the interglobular domain that were susceptible to cleavage by MT1-MMP. Degradation products were identified by Western blotting with neo-epitope antibodies specific for MMP-derived N- and C-terminal sequences. The results showed that MT1-MMP cleaved at the N341-F342 and D441-L442 bonds, as shown for other MMPs, and also at a site 13 amino acids C-terminal to the N341-F342 site. The G2 product of this additional cleavage was identified by sequence analysis and revealed an N-terminus commencing T355VxxPDVELPLP. The data are consistent with MT1-MMP cleavage at three sites in the aggrecan interglobular domain; one at N342-F342, a second at D441-L442 and a third at Q354-T355.
Fosang
A J
AJ
Orthopaedic Molecular Biology Research Unit, Melbourne University, Royal Children's Hospital, Parkville, Australia. fosang@cryptic.rch.unimelb.edu.au
Last
K
K
Fujii
Y
Y
Seiki
M
M
Okada
Y
Y
D053674:Aggrecans; D000595:Amino Acid Sequence; D016326:Extracellular Matrix Proteins; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry; D011509:Proteoglycans / Q000737:chemistry*; D017421:Sequence Analysis
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011509:Proteoglycans; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2