Structural and functional evidence for a substrate exclusion mechanism in mammalian tolloid like-1 (TLL-1) proteinase

Richard Berry, Thomas A Jowitt, Laure Garrigue-Antar, Karl E. Kadler, Clair Baldock

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

Bone morphogenetic protein-1 (BMP-1)/tolloid proteinases are fundamental to regulating dorsal ventral patterning and extracellular matrix deposition. In mammals there are four proteinases, the splice variants BMP-1 and mammalian tolloid (mTLD), and tolloid like-1 and -2 (TLL-1/2). BMP-1 has the highest catalytic activity and lacks three non-catalytic domains. We demonstrate that TLL-1, which has intermediate activity, forms a calcium-ion dependent dimer with monomers stacked side-by-side. In contrast, truncated TLL-1 molecules having the same shorter structure as BMP-1 are monomers and have improved activity towards their substrate chordin. The increased activity exceeds not only that of full-length TLL-1 but also BMP-1.

Original languageEnglish
Pages (from-to)657-661
Number of pages5
JournalFEBS Letters
Volume584
Issue number4
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

Keywords

  • Analytical ultracentrifugation
  • Chordin
  • Pro-collagen C-proteinase
  • Tolloid

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