COLLAGEN BIOSYNTHESIS IN CONNECTIVE TISSUE DISEASE

胶原蛋白是人体内的主要结构蛋白， 例如皮肤、骨、腱、软骨、肺 角膜和心脏瓣膜 正常的胶原蛋白生物合成需要 严格调控许多转录，翻译， 和翻译后事件，包括类型特异性合成， 脯氨酰和赖氨酰残基的羟基化， 羟赖氨酰残基，二硫键形成，分泌， 延伸肽的切割、原纤维形成和交联。 在这个连续过程中的任何一个步骤中的扰动可能是 预期会导致胶原蛋白结构改变，因此 与之相关的疾病。胶原蛋白结构缺失或 已知生物合成发生在许多结缔组织中 疾病如Ehlers-Danlos综合征、成骨 马凡氏综合征和皮肤拉克萨。 我们建议 分离赖氨酰羟化酶的cDNA，以阐明 VI型埃勒斯酶缺陷的分子机制- 丹洛斯综合征。 我们还建议将突变的特征 导致在一个细胞中合成异常的2（I）胶原蛋白链， 马凡氏综合征患者

Collagen is a major structural protein in the body, providing the framework for tissues such as skin, bone, tendon, cartilage, lung, cornea, and heart valve. Normal collagen biosynthesis requires a stringent regulation of a number of transcriptional, translational, and post-translational events including type-specific synthesis, hydroxylation of prolyl and Iysyl residues, glycosylation of hydroxylysyl residues, disulfide bond formation, secretion, cleavage of extension peptides, fibril formation, and cross-linking. Perturbation in any one step in this sequential process might be expected to result in structurally altered collagen, hence the disease associated with it. Abnormalities in collagen structure or biosynthesis are known to occur in a number of connective tissue diseases such as the Ehlers-Danlos syndrome, osteogenesis imperfecta, the Marfan syndrome, and cutis laxa. We propose to isolate a cDNA for lysyl hydroxylase in order to elucidate the molecular mechanism(s) of the enzyme defect in Type VI Ehlers- Danlos syndrome. We also propose to characterize the mutation causing the synthesis of an abnormal 2(I) collagen chain in a patient with the Marfan syndrome.