COLLAGEN BIOSYNTHESIS IN CONNECTIVE TISSUE DISEASE

胶原蛋白是人体内的一种主要结构蛋白，提供 皮肤、骨、肌腱、软骨、肺等组织的支架， 角膜和心脏瓣膜。正常的胶原蛋白生物合成需要 对许多转录、翻译、 和翻译后事件，包括特定类型的合成， 脯氨基和赖氨基残基的羟基化，糖基化 羟基残基，二硫键形成，分泌物， 延伸肽的裂解、原纤维的形成和交联化。 在这个顺序过程中的任何一个步骤中的扰动可能是 预计会导致胶原蛋白结构改变，因此 与之相关的疾病。胶原蛋白结构异常或 已知生物合成发生在许多结缔组织中 埃勒斯-丹洛斯综合征、成骨等疾病 不完美，马凡综合征和皮肤松弛。我们建议 分离赖氨酸羟基酶基因，以阐明赖氨酰羟基酶的功能 VI型Ehler酶缺陷的分子机制(S) 丹洛斯综合征。我们还建议对突变进行表征 导致一种异常的2(I)胶原链的合成 马凡综合征患者。

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.