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

doi:10.1073/pnas.091601698

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

^*Department of Molecular and Cell Biology, 229 Stanley Hall, University of California, Berkeley, CA 94720; and ^†DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304

Edited by James A. Wells, Sunesis Pharmaceuticals, Inc., Redwood City, CA, and approved March 6, 2001 (received for review December 20, 2000)

Abstract

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-Å 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.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Department of Molecular and Cell Biology, Stanley/Donner ASU, 229 Stanley Hall No. 3206, University of California, Berkeley, CA 94720-3206. E-mail: handel{at}paradise1.berkeley.edu.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank (PDB ID code 1I1J).
Abbreviations:

MIA,

melanoma inhibitory activity;

PPII,

polyproline type II;

SH3,

Src homology 3