A BRET-based assay reveals collagen-Hsp47 interaction dynamics in the endoplasmic reticulum and small-molecule inhibition of this interaction.

ABSTRACT: Molecular chaperones perform pivotal roles in proteostasis by engaging in protein-protein interactions (PPIs). The collagen-specific molecular chaperone Hsp47 (heat shock protein 47) interacts with procollagen in the endoplasmic reticulum (ER) and plays crucial roles in collagen synthesis. PPIs between Hsp47 and collagen could offer a therapeutic target for fibrosis, which is characterized by abnormal collagen accumulation in the extracellular matrix of fibrotic organs. Herein, we established a bioluminescence resonance energy transfer (BRET) system for assessing Hsp47-collagen interaction dynamics within the ER. After optimization and validation of the method, we could demonstrate inhibition of the interaction between Hsp47 and collagen by a small molecule (Col003) in the ER. Using the BR

SUBMITTER: Ito S 

PROVIDER: S-EPMC6827286 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature