Mutants of collagen-specific molecular chaperone Hsp47 causing osteogenesis imperfecta are structurally unstable with weak binding affinity to collagen.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragile bones. Most OI cases are caused by defects in type I collagen structure or synthesis. Mutations in collagen specific molecular chaperone Hsp47, specifically L78P and L326P, lead to OI, yet these mutants are not fully characterized. Here, we found that both Hsp47 mutants were structurally unstable and formed high molecular weight complexes. They were degraded by the ubiquitin-proteasome system, and the collagen-binding ability of the mutants was significantly lower than that of the wild type. Although the chemical chaperone 4-PBA partially restores the solubility of the Hsp47 OI mutants, collagen-binding activity of Hsp47 was not improved.