title: Structural and functional evidence for a substrate exclusion mechanism in mammalian tolloid like-1 (TLL-1) proteinase.
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.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Berry
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jowitt
authors.forename: Laure
authors.initials: L
authors.lastname: Garrigue-Antar
authors.forename: Karl E
authors.initials: KE
authors.lastname: Kadler
authors.forename: Clair
authors.initials: C
authors.lastname: Baldock
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D055394:Tolloid-Like Metalloproteinases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C054234:chordin; D055394:Tolloid-Like Metalloproteinases; C484478:TLL1 protein, human; D002118:Calcium