Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development.
Prolyl 3-hydroxylase 1 (P3H1), cartilage-associated protein (CRTAP) and cyclophilin B (CyPB) form a complex in the endoplasmic reticulum which is responsible for 3-hydroxylation of a limited number of proline residues in types I, II and V collagens. In this complex, CRTAP serves the role of helper protein, while P3H1 provides the enzymatic activity for the modification. In type I collagen, the major protein of the extracellular matrix of bone, the complex 3-hydroxylates only the a1(I)Pro986 residue. P3H1 and CRTAP each also have independent roles as components of matrix. Furthermore, the two proteins have significant homology with each other. The critical importance of the components of the complex for normal bone development has been revealed by a Crtap knock-out mouse and by infants and children with null mutations of CRTAP and LEPRE1, the gene that encodes P3H1. On a clinical level, defects in the components of the prolyl 3-hydroxylation complex have been shown to be the long-sought cause of severe and lethal recessive osteogenesis imperfecta.
Marini
Joan C
JC
Bone and Extracellular Matrix Branch, The National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. oidoc@helix.nih.gov
Cabral
Wayne A
WA
Barnes
Aileen M
AM
Chang
Weizhong
W
D000595:Amino Acid Sequence; D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000473:pathology / Q000502:physiology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D064828:Prolyl Hydroxylases; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
C108053:CRTAP protein, human; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D011509:Proteoglycans; C081786:cyclophilin B; D064828:Prolyl Hydroxylases; C485657:P3H1 protein, human; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase