Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue, and these distinct hydroxylation patterns modulate collagen cross-linking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis, and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2); however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65, and BiP regulating the activity of LH2. Our findings show that FKBP65 and HSP47 modulate the activity of LH2 to either favor or repress its activity. BiP was also identified as a member of the complex, playing a role in enhancing the formation of the complex. This newly identified ER chaperone complex contributes to our understanding of how LH2 regulates lysyl hydroxylation of type I collagen C-telopeptides to affect the quality of connective tissues. © 2017 American Society for Bone and Mineral Research.

Department of Biology Faculty of Medicine Masaryk University International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Department of Human Genetics David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA

Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA

Department of Molecular Cell and Developmental Biology University of California at Los Angeles Los Angeles CA USA

Department of Obstetrics and Gynecology David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA

Department of Orthopaedic Surgery David Geffen School of Medicine University of California at Los Angeles Los Angeles CA USA

Department of Orthopaedics and Sports Medicine University of Washington Seattle WA USA

Faculty of Science University of South Bohemia Ceske Budejovice Czech Republic

Howard Hughes Medical Institute Chevy Chase MD USA

Networking Research Center on Bioengineering Biomaterials and Nanomedicine University of Malaga Malaga Spain

Pediatric Genetics Unit Department of Pediatrics Acibadem University School of Medicine Istanbul Turkey

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