Three-dimensional Solution Structure of Bombyxin-II an Insulin-like Peptide of the SilkmothBombyx mori: Structural Comparison with Insulin and Relaxin

Koji Nagata, Hideki Hatanaka, Daisuke Kohda, Hiroshi Kataoka, Hiromichi Nagasawa, Akira Isogai, Hironori Ishizaki, Akinori Suzuki, Fuyuhiko Inagaki

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Abstract

The three-dimensional solution structure of bombyxin-II, an insulin-like two-chain peptide produced by the brain of the silkwormBombyx morihas been determined by simulated annealing calculations based on 535 distance constraints and 24 torsion-angle constraints derived from NMR data and three distance constraints of the disulfide bonds. To our knowledge, this is the first three-dimensional structure determined for an invertebrate insulin-related peptide. The root-mean-square deviations between the best 10 structures and the mean structure are 0.58(±0.15) Å for the backbone heavy atoms (N, CαC) and 1.03(±0.18) Å 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 overall main-chain structure of bombyxin-II is similar to that of insulin. However, there are significant conformational and functional differences 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 that of relaxin and is not required for bombyxin activity, while the corresponding part of insulin adopts a sharp turn and a β-strand and is essential for insulin activity. This structure demonstrates that bombyxin-II is more closely related to relaxin than to insulin, and suggests that insulin might have evolved the additional receptor-recognition site in the B-chain C-terminal β-strand to distinguish itself from bombyxin and relaxin. The structure of bombyxin-II thus provides novel insights into the receptor recognition and divergent molecular evolution of insulin-super family peptides.

Original languageEnglish
Pages (from-to)749-758
Number of pages10
JournalJournal of Molecular Biology
Volume253
Issue number5
DOIs
Publication statusPublished - Nov 10 1995
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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