Substrate recognition of collagen-specific molecular chaperone HSP47. Structural requirements and binding regulation

Takaki Koide, Shinichi Asada, Kazuhiro Nagata

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Prior to secretion, procollagen molecules are correctly folded to triple helices in the endoplasmic reticulum (ER). HSP47 specifically associates with procollagen in the ER during its folding and/or modification processes and is thought to function as a collagen-specific molecular chaperone (Nagata, K. (1996) Trends Biochem. Sci. 21, 23-26). However, structural requirements for substrate recognition and regulation of the binding have not yet been elucidated. Here, we show that a typical collagen model sequence, (Pro-Pro- Gly)(n), possesses sufficient structural information required for recognition by HSP47. A structure-activity relationship study using synthetic analogs of (Pro-Pro-Gly)(n) has revealed the requirements in both chain length and primary structure for the interaction. The substrate recognition of HSP47 has also been shown to be similar but distinct from that of prolyl 4-hydroxylase, an ER resident enzyme. Further, it has shown that the interaction of HSP47 with the substrate peptides is abolished by prolyl 4-hydroxylation of the second Pro residues in Pro-Pro-Gly triplets and that the fully prolyl 4- hydroxylated peptide, (Pro-Hyp-Gly)(n), does not interact with HSP47. We thus have proposed a model in which HSP47 dissociates from procollagen during the process of prolyl 4-hydroxylation in the ER.

Original languageEnglish
Pages (from-to)34523-34526
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number49
DOIs
Publication statusPublished - 1999 Dec 3
Externally publishedYes

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prolyl-prolyl-glycine
Procollagen
Molecular Chaperones
Endoplasmic Reticulum
Hydroxylation
Collagen
Substrates
Prolyl Hydroxylases
Peptides
Chain length
Structure-Activity Relationship
Molecules
Enzymes
poly(prolylprolylglycine)15

ASJC Scopus subject areas

  • Biochemistry

Cite this

Substrate recognition of collagen-specific molecular chaperone HSP47. Structural requirements and binding regulation. / Koide, Takaki; Asada, Shinichi; Nagata, Kazuhiro.

In: Journal of Biological Chemistry, Vol. 274, No. 49, 03.12.1999, p. 34523-34526.

Research output: Contribution to journalArticle

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