CRTAP Is Required for Prolyl 3- Hydroxylation and Mutations Cause Recessive Osteogenesis Imperfecta

Roy Morello, Terry K. Bertin, Yuqing Chen, John Hicks, Laura Tonachini, Massimiliano Monticone, Patrizio Castagnola, Frank Rauch, Francis H. Glorieux, Janice Vranka, Hans Peter Bächinger, James M. Pace, Ulrike Schwarze, Peter H. Byers, Mary Ann Weis, Russell J. Fernandes, David R. Eyre, Zhenqiang Yao, Brendan F. Boyce, Brendan Lee

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414 Scopus citations


Prolyl hydroxylation is a critical posttranslational modification that affects structure, function, and turnover of target proteins. Prolyl 3-hydroxylation occurs at only one position in the triple-helical domain of fibrillar collagen chains, and its biological significance is unknown. CRTAP shares homology with a family of putative prolyl 3-hydroxylases (P3Hs), but it does not contain their common dioxygenase domain. Loss of Crtap in mice causes an osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production. CRTAP can form a complex with P3H1 and cyclophilin B (CYPB), and Crtap-/- bone and cartilage collagens show decreased prolyl 3-hydroxylation. Moreover, mutant collagen shows evidence of overmodification, and collagen fibrils in mutant skin have increased diameter consistent with altered fibrillogenesis. In humans, CRTAP mutations are associated with the clinical spectrum of recessive osteogenesis imperfecta, including the type II and VII forms. Hence, dysregulation of prolyl 3-hydroxylation is a mechanism for connective tissue disease.

Original languageEnglish (US)
Pages (from-to)291-304
Number of pages14
Issue number2
StatePublished - Oct 20 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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