Mammalian tolloid-like 1 binds procollagen C-proteinase enhancer protein 1 and differs from bone morphogenetic protein 1 in the functional roles of homologous protein domains

The Journal of Biological Chemistry
Gaoxiang GeD S Greenspan

Abstract

Bone morphogenetic protein 1 (BMP1) is the prototype of a subgroup of metalloproteinases with manifold roles in morphogenesis. Four mammalian subgroup members exist, including BMP1 and mammalian Tolloid-like 1 (mTLL1). Subgroup members have a conserved protein domain structure: an NH2-terminal astacin-like protease domain, followed by a fixed order of CUB and epidermal growth factor-like protein-protein interaction motifs. Previous structure/function studies have documented those BMP1 protein domains necessary for secretion, and activity against various substrates. Here we demonstrate that, in contradiction to previous reports, the most NH2-terminal CUB domain (CUB1) is not required for BMP1 secretion nor is the next CUB domain (CUB2) required for enzymatic activity. The same is true for mTLL1. In fact, secreted protease domains of BMP1 and mTLL1, devoid of CUB or epidermal growth factor-like domains, have procollagen C-proteinase (pCP) activity and activity for biosynthetic processing of biglycan, the latter with kinetics superior to those of the full-length proteins. Structure-function analyses herein also suggest differences in the functional roles played by some of the homologous domains in BMP1 and mTLL1. Surprisingly, alt...Continue Reading

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Citations

May 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Richard BerryClair Baldock
Jul 21, 2009·The Journal of Biological Chemistry·Guorui HuangDaniel S Greenspan
Oct 6, 2009·The Journal of Biological Chemistry·Daniel KronenbergCatherine Moali
Mar 9, 2010·The Journal of Biological Chemistry·Mourad BekhoucheCatherine Moali
Oct 27, 2011·The Journal of Biological Chemistry·Alison Muir, Daniel S Greenspan
Oct 21, 2009·Journal of Tissue Engineering and Regenerative Medicine·Rosmarie HardmeierStefan Marlovits
Oct 15, 2013·The Biochemical Journal·Romain SalzaSylvie Ricard-Blum
Mar 19, 2011·Journal of the American Society of Nephrology : JASN·Hirokazu Okada
Jul 31, 2008·The Journal of Biological Chemistry·Timothy J Geach, Leslie Dale
Oct 2, 2019·European Journal of Human Genetics : EJHG·Talal AlanziFowzan S Alkuraya
Jul 16, 2016·Circulation. Cardiovascular Genetics·Stephanie LaHayeVidu Garg

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