CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta.
Cell
; 127(2): 291-304, 2006 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-17055431
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis Imperfecta
/
Proteínas
/
Proteínas de la Matriz Extracelular
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Procolágeno-Prolina Dioxigenasa
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Mutación
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos