Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites.

Brevican is a member of the lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system. The susceptibility of brevican to digestion by matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9, -10, and -13 and membrane type 1 and 3 MMPs) and aggrecanase-1 (ADAMTS4) was ...
examined. MMP-1, -2, -3, -7, -8, -10, and -13 degraded brevican into a few fragments with similar molecular masses, whereas the degradation products of aggrecanase-1 had apparently different sizes. NH(2)-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain. MMP-1, -2, -3, -7, -8, -10, and -13 preferentially attacked the Ala(360)-Phe(361) bond, whereas aggrecanase-1 cleaved the Glu(395)-Ser(396) bond, which are similar to the cleavage sites observed with cartilage proteoglycan (aggrecan) for the MMPs and aggrecanase-1, respectively. These data demonstrate that MMP-1, -2, -3, -7, -8, -10, and -13 and aggrecanase-1 digest brevican in a similar pattern to aggrecan and suggest that they may be responsible for the physiological turnover and pathological degradation of brevican.
Mesh Terms:
ADAM Proteins, Amino Acid Sequence, Animals, Binding Sites, CHO Cells, Cricetinae, Humans, Kinetics, Lectins, C-Type, Metalloendopeptidases, Molecular Sequence Data, Nerve Tissue Proteins, Peptide Fragments, Procollagen N-Endopeptidase, Proteochondroitin Sulfates, Rats, Recombinant Proteins, Substrate Specificity, Transfection
J. Biol. Chem.
Date: Dec. 08, 2000
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