The structural basis for the elastolytic activity of the 92-kDa and 72-kDa gelatinases: Role of the fibronectin type II-like repeats

J. Michael Shipley, Glenn A.R. Doyle, Catherine J. Fliszar, Qi Zhuang Ye, Linda L. Johnson, Steven D. Shapiro, Howard G. Welgus, Robert M. Senior

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166 Scopus citations

Abstract

Several matrix metalloproteinases, including the 92-kDa and 72-kDa gelatinases, macrophage metalloelastase (MME), and matrilysin degrade insoluble elastin. Because elastolytieally active MME and matrilysin consist only of a catalytic domain (CD), we speculated that the homologous CDs of the 92-kDa and 72-kDa gelatinases would confer their elastolytic activities. In contrast to the MME CD, the 92 and 72 CDs expressed in Escherichia coli (lacking the internal fibronectin type II-like repeats) had no elastase activity, although both were gelatinolytic and cleaved a thiopeptolide substrate at rates comparable to the full-length gelatinases. To test the role of the fibronectin type II-like repeats in elastolytic activity, we expressed the 92-kDa gelatinase CD with its fibronectin type II-like repeats (92 CD/FN) in yeast. 92 CD/FN degraded insoluble elastin with activity comparable to full-length 92-kDa gelatinase. 92 and 72 CDs lacking the fibronectin type II-like repeats did not bind elastin, whereas the parent enzymes and 92 CD/FN did bind elastin. Furthermore, recombinant 92-kDa fibronectin type II-like repeats inhibited binding of the 92-kDa gelatinase to elastin. We conclude that the 92-and 72-kDa gelatinases require the fibronectin type II-like repeats for elastase activity.

Original languageEnglish (US)
Pages (from-to)4335-4341
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number8
DOIs
StatePublished - Feb 23 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Shipley, J. M., Doyle, G. A. R., Fliszar, C. J., Ye, Q. Z., Johnson, L. L., Shapiro, S. D., Welgus, H. G., & Senior, R. M. (1996). The structural basis for the elastolytic activity of the 92-kDa and 72-kDa gelatinases: Role of the fibronectin type II-like repeats. Journal of Biological Chemistry, 271(8), 4335-4341. https://doi.org/10.1074/jbc.271.8.4335