Qabar, AzizDerick, LauraLawler, JackDixit, Vishva2019-10-051995Qabar, Aziz, Laura Derick, Jack Lawler, and Vishva Dixit. 1995. “Thrombospondin 3 Is a Pentameric Molecule Held Together by Interchain Disulfide Linkage Involving Two Cysteine Residues.” Journal of Biological Chemistry 270 (21): 12725–29. https://doi.org/10.1074/jbc.270.21.12725.0021-92581083-351Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483236The 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.en-USJournal Article2019-10-0510.1074/jbc.270.21.12725