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

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 high...

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Bibliographic Details
Published in:FEBS letters 2010-02, Vol.584 (4), p.657-661
Main Authors: Berry, Richard, Jowitt, Thomas A., Garrigue-Antar, Laure, Kadler, Karl E., Baldock, Clair
Format: Article
Language:English
Subjects:
Analytical ultracentrifugation
Animals
Biochemistry
Biochemistry, Molecular Biology
Calcium - metabolism
Catalysis
Cell Line
Chordin
Electrophoresis, Polyacrylamide Gel
Glycoproteins - metabolism
Humans
Intercellular Signaling Peptides and Proteins - metabolism
Kinetics
Life Sciences
Microscopy, Electron, Transmission
Models, Molecular
Molecular biology
Pro-collagen C-proteinase
Protein Multimerization
Protein Structure, Quaternary
Protein Structure, Tertiary
Structural Biology
Substrate Specificity
Tolloid
Tolloid-Like Metalloproteinases - chemistry
Tolloid-Like Metalloproteinases - metabolism
Tolloid-Like Metalloproteinases - ultrastructure
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Summary: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. MINT-7386098: BMP-1 (uniprotkb:P13497) cleaves (MI:0194) Chordin (uniprotkb:Q9H2X0) by protease assay (MI:0435)
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2009.12.050