A Chaperone Complex Formed by HSP47, FKBP65, and BiP Modulates Telopeptide Lysyl Hydroxylation of Type I Procollagen.
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 Orthopaedic Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.|Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), University of Malaga, Malaga, Spain.
Ivan
I
Duran
Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Jorge H
JH
Martin
Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, USA.
Mary Ann
MA
Weis
Department of Biology, Faculty of Medicine, Masaryk University, International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Pavel
P
Krejci
Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic.
Peter
P
Konik
Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, USA.
Bing
B
Li
Pediatric Genetics Unit, Department of Pediatrics, Acibadem University School of Medicine, Istanbul, Turkey.
Yasemin
Y
Alanay
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Caressa
C
Lietman
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Brendan
B
Lee
Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, USA.
David
D
Eyre
Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.|Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, USA.
Daniel H
DH
Cohn
Department of Human Genetics, David Geffen School of Medicine, 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.
Deborah
D
Krakow
D000818:Animals; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004795:Enzyme Stability; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism*; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000378:metabolism; D020349:Surface Plasmon Resonance; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*
D024042:Collagen Type I; D000091342:Endoplasmic Reticulum Chaperone BiP; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D046912:Multiprotein Complexes; D010455:Peptides; D011347:Procollagen; C494660:SERPINH1 protein, human; C052929:collagen type I trimeric cross-linked peptide; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human; D008239:Lysine