Identification of the Receptor-recognition Surface of Bombyxin-II, an Insulin-like Peptide of the SilkmothBombyx mori: Critical Importance of the B-chain Central Part

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Bombyxin-II, a brain-secretory peptide of the silkmothBombyx mori, shares 40% sequence identity and the characteristics core structure with human insulin. In spite of the structural similarity, no cross-activity is observed between them. To localize the active region of bombyxin-II, we have synthesized chimeric molecules of bombyxin-II and human insulin, and examined their bombyxin activity. Two chimeric molecules, which were sequentially identical except for the B-chain central part, showed significantly different potencies in bombyxin activity. Solution structure determination of these chimeric molecules revealed that their B-chain central parts took similar main-chain conformation, but formed dissimilar patches on their molecular surfaces. Therefore, the surface patch formed by the central part of the bombyxin-II B-chain is of critical importance for recognition of the bombyxin receptor. The above results, together with other data on the structure-activity relationships of bombyxin, indicate that the receptor-recognition surface of bombyxin-II includes the A-chain N and C, termini in addition to the B-chain central part. Though bombyxin-II, human insulin and human relaxin 2 use the common surface as their receptor-recognition sites, each of the surface patches is characterized by the variety of involved side-chains. Insulin and relaxin involve additional parts for receptor recognition, particularly the B-chain C-terminal part and the extended A-chain N-terminal helix, respectively. In conclusion, these ligands have evolved their own specific mechanisms for receptor recognition while retaining the major recognition surface.

Original languageEnglish
Pages (from-to)759-770
Number of pages12
JournalJournal of Molecular Biology
Volume253
Issue number5
DOIs
Publication statusPublished - Nov 10 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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