NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.

Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological importa...

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Autores principales:	Maho Yagi-Utsumi, Sumi Yoshikawa, Yoshiki Yamaguchi, Yohei Nishi, Eiji Kurimoto, Yoshihito Ishida, Takayuki Homma, Jun Hoseki, Yoshimi Nishikawa, Takaki Koide, Kazuhiro Nagata, Koichi Kato
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5dae327d8d044f7b90243b47228b1f84
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spelling	oai:doaj.org-article:5dae327d8d044f7b90243b47228b1f842021-11-18T08:14:07ZNMR and mutational identification of the collagen-binding site of the chaperone Hsp47.1932-620310.1371/journal.pone.0045930https://doaj.org/article/5dae327d8d044f7b90243b47228b1f842012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049894/?tool=EBIhttps://doaj.org/toc/1932-6203Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological importance, little is currently known about the collagen-binding mode of Hsp47 from a structural aspect. Here, we describe an NMR study that was conducted to identify the collagen-binding site of Hsp47. We used chicken Hsp47, which has higher solubility than its human counterpart, and applied a selective (15)N-labeling method targeting its tryptophan and histidine residues. Spectral assignments were made based on site-directed mutagenesis of the individual residues. By inspecting the spectral changes that were observed upon interaction with a trimeric collagen peptide and the mutational data, we successfully mapped the collagen-binding site in the B/C β-barrel domain and a nearby loop in a 3D-homology model based upon a serpin fold. This conclusion was confirmed by mutational analysis. Our findings provide a molecular basis for the design of compounds that target the interaction between Hsp47 and procollagen as therapeutics for fibrotic diseases.Maho Yagi-UtsumiSumi YoshikawaYoshiki YamaguchiYohei NishiEiji KurimotoYoshihito IshidaTakayuki HommaJun HosekiYoshimi NishikawaTakaki KoideKazuhiro NagataKoichi KatoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45930 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maho Yagi-Utsumi Sumi Yoshikawa Yoshiki Yamaguchi Yohei Nishi Eiji Kurimoto Yoshihito Ishida Takayuki Homma Jun Hoseki Yoshimi Nishikawa Takaki Koide Kazuhiro Nagata Koichi Kato NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
description	Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological importance, little is currently known about the collagen-binding mode of Hsp47 from a structural aspect. Here, we describe an NMR study that was conducted to identify the collagen-binding site of Hsp47. We used chicken Hsp47, which has higher solubility than its human counterpart, and applied a selective (15)N-labeling method targeting its tryptophan and histidine residues. Spectral assignments were made based on site-directed mutagenesis of the individual residues. By inspecting the spectral changes that were observed upon interaction with a trimeric collagen peptide and the mutational data, we successfully mapped the collagen-binding site in the B/C β-barrel domain and a nearby loop in a 3D-homology model based upon a serpin fold. This conclusion was confirmed by mutational analysis. Our findings provide a molecular basis for the design of compounds that target the interaction between Hsp47 and procollagen as therapeutics for fibrotic diseases.
format	article
author	Maho Yagi-Utsumi Sumi Yoshikawa Yoshiki Yamaguchi Yohei Nishi Eiji Kurimoto Yoshihito Ishida Takayuki Homma Jun Hoseki Yoshimi Nishikawa Takaki Koide Kazuhiro Nagata Koichi Kato
author_facet	Maho Yagi-Utsumi Sumi Yoshikawa Yoshiki Yamaguchi Yohei Nishi Eiji Kurimoto Yoshihito Ishida Takayuki Homma Jun Hoseki Yoshimi Nishikawa Takaki Koide Kazuhiro Nagata Koichi Kato
author_sort	Maho Yagi-Utsumi
title	NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
title_short	NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
title_full	NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
title_fullStr	NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
title_full_unstemmed	NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
title_sort	nmr and mutational identification of the collagen-binding site of the chaperone hsp47.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5dae327d8d044f7b90243b47228b1f84
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NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.

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