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

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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

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Morus
Insulin
Peptides
Relaxin
Structure-Activity Relationship
bombyxin II
Ligands
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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

In: Journal of Molecular Biology, Vol. 253, No. 5, 10.11.1995, p. 759-770.

Research output: Contribution to journalArticle

Nagata, Koji ; Hatanaka, Hideki ; Kohda, Daisuke ; Kataoka, Hiroshi ; Nagasawa, Hiromichi ; Isogai, Akira ; Ishizaki, Hironori ; Suzuki, Akinori ; Inagaki, Fuyuhiko. / 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. In: Journal of Molecular Biology. 1995 ; Vol. 253, No. 5. pp. 759-770.
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