A structure-activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP47

Yoshimi Nishikawa, Yoshifumi Takahara, Shinichi Asada, Akira Shigenaga, Akira Otaka, Kouki Kitagawa, Takaki Koide

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Heat-shock protein 47 (HSP47) is a chaperone that facilitates the proper folding of procollagen. Our previous studies showed that the high-affinity HSP47-binding motif in the collagen triple helix is Xaa-(Thr/Pro)-Gly-Xaa-Arg-Gly. In this study, we further investigated structural requirements for the HSP47-binding motif, using synthetic triple-helical collagen-model peptides with systematic amino acid substitutions at either the Thr/Pro (=Yaa-3) or the Arg (=Yaa0) position. Results obtained from in vitro binding assays indicated that HSP47 detects the side-chain structure of Arg at the Yaa0-position, while the Yaa-3 amino acid serves as the secondary recognition site that affects affinity to HSP47.

    Original languageEnglish
    Pages (from-to)3767-3775
    Number of pages9
    JournalBioorganic and Medicinal Chemistry
    Volume18
    Issue number11
    DOIs
    Publication statusPublished - 2010 Jun 1

    Fingerprint

    HSP47 Heat-Shock Proteins
    Structure-Activity Relationship
    Collagen
    Protein Binding
    Amino Acids
    Procollagen
    Amino Acid Substitution
    Assays
    Substitution reactions
    Peptides

    Keywords

    • Chaperone
    • Collagen
    • Heat-shock protein 47 (HSP47)
    • Peptide

    ASJC Scopus subject areas

    • Pharmaceutical Science
    • Drug Discovery
    • Organic Chemistry
    • Molecular Medicine
    • Molecular Biology
    • Clinical Biochemistry
    • Biochemistry

    Cite this

    A structure-activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP47. / Nishikawa, Yoshimi; Takahara, Yoshifumi; Asada, Shinichi; Shigenaga, Akira; Otaka, Akira; Kitagawa, Kouki; Koide, Takaki.

    In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 11, 01.06.2010, p. 3767-3775.

    Research output: Contribution to journalArticle

    Nishikawa, Yoshimi ; Takahara, Yoshifumi ; Asada, Shinichi ; Shigenaga, Akira ; Otaka, Akira ; Kitagawa, Kouki ; Koide, Takaki. / A structure-activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP47. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 11. pp. 3767-3775.
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    AU - Otaka, Akira

    AU - Kitagawa, Kouki

    AU - Koide, Takaki

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