Role of the netrin-like domain of procollagen C-proteinase enhancer-1 in the control of metalloproteinase activity.

Journal article

The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments.

Authors: Bekhouche, M; Kronenberg, D; Vadon-Le Goff, S; Bijakowski, C; Lim, N

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 285
• Issue: 21
• Pages: 15950-15959
• Publication date: 2010-05-01
• DOI: 10.1074/jbc.m109.086447
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Glycoproteins; Procollagen; Humans; Extracellular Matrix Proteins; Cell Line; Tissue Inhibitor of Metalloproteinases; Tolloid-Like Metalloproteinases; ADAM Proteins; Protein Structure, Tertiary