CRYSTALLIZATION OF THE FIRST 3 DOMAINS OF THE HUMAN INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR

The insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinas e receptor of central importance in cell proliferation. A fragment (re sidues 1-462) comprising the L1-cysteine rich-L2 domains of the human IGF-IR ectodomain has been overexpressed in glycosylation-deficient Le c8 cells and has been affinity-purified via a c-myc tag followed by ge l filtration. The fragment was recognized by two anti-IGF-1R monoclona l antibodies, 24-31 and 24-60, but showed no detectable binding of IGF -1 or IGF-2. Isocratic elution of IGF-1R/462 on anion-exchange chromat ography reduced sample heterogeneity, permitting the production of cry stals that diffracted to 2.6 Angstrom resolution with cell dimensions a = 77.0 Angstrom, b = 99.5 Angstrom, c = 120.1 Angstrom, and space gr oup P2(1)2(1)2(1).