Calcium indirectly regulates immunochemical reactivity and functional activities of the N-domain of thrombospondin-1.
Matrix Biol
; 27(4): 339-51, 2008 May.
Article
in En
| MEDLINE
| ID: mdl-18226512
ABSTRACT
Conformational changes induced in thrombospondin-1 by removal of calcium regulate interactions with some ligands of its N-modules. Because calcium binds primarily to elements of the C-terminal signature domain of thrombospondin-1, which are distant from the N-modules, such regulation was unexpected. To clarify the mechanism for this regulation, we compared ligand binding to the N-modules of thrombospondin-1 in the full-length protein and recombinant trimeric thrombospondin-1 truncated prior to the signature domain. Three monoclonal antibodies were identified that recognize the N-modules, two of which exhibit calcium-dependent binding to native thrombospondin-1 but not to the truncated trimeric protein. These antibodies or calcium selectively modulate interactions of fibronectin, heparin, sulfatide, alpha3beta1 integrin, tumor necrosis factor-alpha-stimulated gene-6 protein, and, to a lesser extent, alpha4beta1 integrin with native thrombospondin-1 but not with the truncated protein. These results indicate connectivity between calcium binding sites in the C-terminal signature domain and the N-modules of thrombospondin-1 that regulates ligand binding and functional activities of the N-modules.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium
/
Thrombospondin 1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Matrix Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2008
Type:
Article
Affiliation country:
United States