3-DIMENSIONAL SOLUTION STRUCTURE OF BOMBYXIN-II AN INSULIN-LIKE PEPTIDE OF THE SILKMOTH BOMBYX-MORI - STRUCTURAL COMPARISON WITH INSULIN AND RELAXIN

The three-dimensional solution structure of bombyxin-II, an insulin-li ke two-chain peptide produced by the brain of the silkworm Bombyx mori , has been determined by simulated annealing calculations based on 535 distance constraints and 24 torsion-angle constraints derived from NM R data and three distance constraints of the disulfide bonds. To our k nowledge, this is the first three-dimensional structure determined for an invertebrate insulin-related peptide. The root-mean-square deviati ons between the best 10 structures and the mean structure are 0.58(+/- 0.15) Angstrom for the backbone heavy atoms (N, C-alpha, C) and 1.03(/-0.18) Angstrom for all non-hydrogen atoms if less well-defined N and C termini (A1, A20, B(-2) to B4 and B23 to B25) are excluded. The ove rall main-chain structure of bombyxin-II is similar to that of insulin . However, there are significant conformational and functional differe nces in their B-chain C-terminal parts. The B-chain C-terminal part of bombyxin-II adopts an extension of the B-chain central helix like tha t of relaxin and is not required for bombyxin activity, while the corr esponding part of insulin adopts a sharp turn and a beta-strand and is essential for insulin activity. This structure demonstrates that bomb yxin-II is more closely related to relaxin than to insulin, and sugges ts that insulin might have evolved the additional receptor-recognition site in the B-chain C-terminal beta-strand to distinguish itself from bombyxin and relaxin. The structure of bombyxin-II thus provides nove l insights into the receptor recognition and divergent molecular evolu tion of insulin-superfamily peptides. (C) 1995 Academic Press Limited