Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development
Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development
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DOI：
10.4161/cc.6.14.4474
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发表时间：
2007-07-15
期刊：
影响因子：
4.3
通讯作者：
Chang, Weizhong
中科院分区：
文献类型：
--
作者：
Marini, Joan C.;Cabral, Wayne A.;Chang, Weizhong
脯氨酰 3-羟化酶 1 (P3H1)、软骨相关蛋白 (CRTAP) 和亲环蛋白 B (CyPB) 在内质网中形成复合物，负责 I、II 和 V 型胶原蛋白中有限数量的脯氨酸残基的 3-羟基化。在该复合物中，CRTAP 发挥辅助蛋白的作用，而 P3H1 则提供修饰的酶活性。在 I 型胶原（骨细胞外基质的主要蛋白质）中，复合物仅 3-羟基化 α 1(I) Pro986 残基。 P3H1和CRTAP作为基质的组成部分也各自具有独立的作用。此外，这两种蛋白质彼此具有显着的同源性。 Crtap 基因敲除小鼠以及 CRTAP 和 LEPRE1（编码 P3H1 的基因）无效突变的婴儿和儿童揭示了复合物成分对正常骨骼发育的至关重要性。在临床水平上，脯氨酰3-羟基化复合物成分的缺陷已被证明是长期寻找的严重和致命的隐性成骨不全的原因。
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 alpha 1(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.