Quality Control of Procollagen in Cells

• Published in: Annual review of biochemistry Vol. 90; no. 1; pp. 631 - 658
• Main Authors: Ito, Shinya, Nagata, Kazuhiro
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 20.06.2021; Annual Reviews, Inc
• Subjects: Animals; Autophagy; Basement membranes; Biosynthesis; Body temperature; Bone strength; Collagen; Collagen - chemistry; Collagen - metabolism; Destabilization; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; ER-phagy; Fibrosis - genetics; Fibrosis - metabolism; Heat shock proteins; HSP47 Heat-Shock Proteins - chemistry; HSP47 Heat-Shock Proteins - genetics; HSP47 Heat-Shock Proteins - metabolism; Humans; Hydroxylation; molecular chaperone Hsp47; Molecular Chaperones - metabolism; Mutation; Phagocytosis; Procollagen; Procollagen - chemistry; Procollagen - metabolism; Proline - chemistry; Proline - metabolism; Protein Conformation; Protein Folding; Protein Processing, Post-Translational; Quality control; Signal transduction; Trimers; triple-helix structure; collagen; triple-helix structure; molecular chaperone Hsp47; quality control; ER-phagy
• ISSN: 0066-4154; 1545-4509
• DOI: 10.1146/annurev-biochem-013118-111603

Collagen is the most abundant protein in mammals. A unique feature of collagen is its triple-helical structure formed by the Gly-Xaa-Yaa repeats. Three single chains of procollagen make a trimer, and the triple-helical structure is then folded in the endoplasmic reticulum (ER). This unique structure is essential for collagen's functions in vivo, including imparting bone strength, allowing signal transduction, and forming basement membranes. The triple-helical structure of procollagen is stabilized by posttranslational modifications and intermolecular interactions, but collagen is labile even at normal body temperature. Heat shock protein 47 (Hsp47) is a collagen-specific molecular chaperone residing in the ER that plays a pivotal role in collagen biosynthesis and quality control of procollagen in the ER. Mutations that affect the triple-helical structure or result in loss of Hsp47 activity cause the destabilization of procollagen, which is then degraded by autophagy. In this review, we present the current state of the field regarding quality control of procollagen.