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 from 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 melanoma metastasis and cartilage development. We report the 1.4-A crystal structure of human MIA, which consists of an Src homology 3 (SH3)-like domain with N- and C-terminal extensions of about 20 aa. each. The N- and C-terminal extensions add additional structural elements to the SH3 domain, forming a previously undescribed fold. MIA is a representative of a recently identified family of proteins and is the first structure of a secreted protein with an SH3 subdomain. The structure also suggests a likely protein interaction site and suggests that, unlike conventional SH3 domains, MIA does not recognize polyproline helices.
Lougheed
J C
JC
Department of Molecular and Cell Biology, 229 Stanley Hall, University of California, Berkeley, CA 94720, USA.
Holton
J M
JM
Alber
T
T
Bazan
J F
JF
Handel
T M
TM
D000595:Amino Acid Sequence; D016326:Extracellular Matrix Proteins; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins