Deletion of epidermal growth factor-like domains converts mammalian tolloid into a chordinase and effective procollagen C-proteinase.

The Journal of Biological Chemistry
L Garrigue-AntarKarl E Kadler

Abstract

Bone morphogenetic protein (BMP)-1 and mammalian tolloid (mTld) are Ca(2+)-dependent metalloproteinases that result from alternative splicing of the bmp1 gene. They have different proteinase activities, e.g. BMP-1 effectively cleaves procollagen (an extracellular matrix protein) and chordin (a BMP antagonist), whereas mTld is a poor procollagen proteinase and will not cleave chordin in the absence of twisted gastrulation. This is perplexing because mTld (being the longer variant) might be expected to cleave all substrates cleaved by BMP-1. Studies have shown that the minimal structure for procollagen proteinase activity is proteinase-CUB1-CUB2 (BMP-1DeltaEC3) and therefore lacking the epidermal growth factor (EGF)-like domain thought to account for the Ca(2+) dependence of BMP-1. In this study we generated three deletion mutants of mTld that lacked either one or both EGF-like domains (referred to as "mTld-DeltaEGF"). The mutated proteins were poorly but sufficiently secreted from 293-EBNA cells for in vitro assays of procollagen and chordin cleavage. Most surprisingly, the mTld-DeltaEGF mutants required Ca(2+) for proteolytic activity, thereby showing that the EGF-like domains do not account for the Ca(2+) dependence of BMP-1/m...Continue Reading

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Citations

Oct 3, 2008·European Journal of Human Genetics : EJHG·Paweł StańczakAleksander L Sieroń
May 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Richard BerryClair Baldock
Oct 27, 2011·The Journal of Biological Chemistry·Alison Muir, Daniel S Greenspan
Apr 2, 2010·Biology of Reproduction·Elizabeth Canty-LairdStéphane Fabre
Nov 3, 2007·Biological Chemistry·Cynthia TallantF Xavier Gomis-Rüth
Apr 20, 2006·Birth Defects Research. Part C, Embryo Today : Reviews·Gaoxiang Ge, Daniel S Greenspan
Jan 19, 2010·Matrix Biology : Journal of the International Society for Matrix Biology·Zofia von Marschall, Larry W Fisher
Feb 21, 2006·The Journal of Biological Chemistry·Elizabeth G CantyKarl E Kadler
May 17, 2017·International Journal of Experimental Pathology·Karl E Kadler
Nov 19, 2020·American Journal of Physiology. Cell Physiology·Elsa-Noah N'DiayeNing Ding

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