Overlapping 9 and 15 mer peptides covering the length of the insulin receptor a-subunit sequence were synthesised and measured for their ability to specifically bind 125I-insulin. The resulting insulin binding sequences were analysed to:
The results indicate at least seven putative insulin-binding regions (R1 to R7) along the length of the insulin receptor and at least six insulin-binding sequence motifs. The amino acid sequence motifs particularly prevalent were (in Prosite format): K-x(0,2)-K; L-x(2,4)-K-x(2,4)-S; C-P-[GT]; and C-x(3,5)-C-x(4,5)-K.
We discuss the possibility that R3 of the insulin receptor (in particular residues 260 to 277) is the putative site of insulinís principal interaction with its receptor and that this interaction is likely to be electrostatic. We also discuss the potential of sequence motifs, and the insulin-binding scoring matrix, to diagnose insulin binding to other peptides or proteins.