Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins

Melanoma inhibitory activity (MIA) is a 12-kDa protein that is secreted fro m both chondrocytes and malignant melanoma cells. MIA has been reported to have effects on cell growth and adhesion, and it may play a role in melanom a metastasis and cartilage development. We report the 1.4-Angstrom crystal structure of human MIA, which consists of an Src homology 3 (SH3)-like doma in with N- and C-terminal extensions of about 20 aa each. The N- and C-term inal extensions add additional structural elements to the SH3 domain, formi ng a previously undescribed fold. MIA is a representative of a recently ide ntified family of proteins and is the first structure of a secreted protein with an SH3 subdomain, The structure also suggests a likely protein intera ction site and suggests that, unlike conventional SH3 domains, MIA does not recognize polyproline helices.