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The extracellular human melanoma inhibitory activity (MIA) protein adopts an SH3 domain‐like fold
Author(s) -
Stoll Raphael,
Renner Christian,
Zweckstetter Markus,
Brüggert Michael,
Ambrosius Dorothee,
Palme Stefan,
Engh Richard A.,
Golob Michaela,
Breibach Ines,
Buettner Reinhard,
Voelter Wolfgang,
Holak Tad A.,
Bosserhoff AnjaKatrin
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.3.340
Subject(s) - library science , art history , classics , art , computer science
Melanoma inhibitory activity (MIA) protein is a clinically valuable marker in patients with malignant melanoma, as enhanced values diagnose metastatic melanoma stages III and IV. Here we show that the recombinant human MIA adopts an SH3 domain‐like fold in solution, with two perpendicular, antiparallel, three‐ and five‐stranded β‐sheets. In contrast to known structures with the SH3 domain fold, MIA is a single‐domain protein, and contains an additional antiparallel β‐sheet and two disulfide bonds. MIA is also the first extracellular protein found to have the SH3 domain‐like fold. Furthermore, we show that MIA interacts with fibronectin and that the peptide ligands identified for MIA exhibit a matching sequence to type III human fibronectin repeats, especially to FN14, which is close to an integrin α 4 β 1 binding site. The present study, therefore, may explain the role of MIA in metastasis in vivo , and supports a model in which the binding of human MIA to type III repeats of fibronectin competes with integrin binding, thus detaching cells from the extracellular matrix.