NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2012-09-25
Start Page
e45930
Journal / Book Title
PLoS One
Volume
7
Issue
9
Copyright Statement
© 2012 Yagi-Utsumi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Description
04.03.14 KB. Ok to add published version to spiral, OA paper.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/23049894
PONE-D-12-08705
Coverage Spatial
United States