title: Thrombospondin 3 is a pentameric molecule held together by interchain disulfide linkage involving two cysteine residues.
abstract: The thrombospondins (TSPs) are a family of 5 distinct gene products designated TSP1, -2, -3, -4, and COMP, for cartilage oligomeric matrix protein. TSP1, the prototypical member, is a trimeric extracellular matrix molecule implicated in cell migration and development. TSP1 trimer formation is mediated by interchain disulfide linkage involving two NH2-terminal cysteines. TSP3, a recent addition to the family, is a developmentally regulated heparin binding protein that is similar in sequence to the COOH terminus of TSP1 but has a distinct NH2 terminus. This has raised the question of the oligomeric nature of TSP3 and identification of the cysteine residues involved in oligomer formation. We demonstrate, using a combination of deletional and site-directed mutagenesis and rotary shadowing electron microscopy, that TSP3, like TSP4 and COMP, is a pentameric molecule. TSP3 is held together by interchain disulfide linkage involving just two cysteine residues, Cys-245 and Cys-248.
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor 48109, USA.
authors.forename: A
authors.initials: A
authors.lastname: Qabar
authors.forename: L
authors.initials: L
authors.lastname: Derick
authors.forename: J
authors.initials: J
authors.lastname: Lawler
authors.forename: V
authors.initials: V
authors.lastname: Dixit
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry; D004252:DNA Mutational Analysis; D004220:Disulfides / Q000737:chemistry; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D064235:Matrilin Proteins; D051379:Mice; D008956:Models, Chemical; D016296:Mutagenesis; D010084:Oxidation-Reduction; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000648:ultrastructure; D017384:Sequence Deletion; D019699:Thrombospondins
chemical_list: D004220:Disulfides; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D011994:Recombinant Proteins; D019699:Thrombospondins; D003545:Cysteine