RHODOPSIN MISFOLDING IN RETINITIS PIGMENTOSA

描述（改编自申请人摘要）：视紫红质突变 基因与RP相关，并且是RP的最常见原因。 70多 突变，大多数是单个氨基酸的变化已被确定， 视紫红质和这些已经在所有三个，椎间盘内， 跨膜和胞质结构域。 研究体内折叠途径 实验室的研究表明， P23 H、G188 R在椎间盘内区域也存在位点特异性突变 作为跨膜螺旋C中的突变L125 R，其已经被 在RP中鉴定的，已经显示出导致相应的 视蛋白 本研究建议中要提出的问题是： （1）在视紫红质中有多少已知的RP突变实际上 导致部分或全部错误折叠，它们的总体后果是什么？ 视觉传导;（2）异常的确切化学性质是什么？ 共价键，一种二硫键，表征RP中的错误折叠 突变体;和（3）可以将错误的二硫键重排为正常的二硫键。 二硫键，其特征在于正确折叠的视蛋白， 在体内可能具有重要意义。

DESCRIPTION (Adapted from applicant's abstract): Mutations in the rhodopsin gene are associated with and are the most common cause of RP. More than 70 mutations, mostly single amino acid changes have been identified in rhodopsin and these have been observed in all the three, intradiscal, transmembrane and cytoplasmic domains. Work on the in vivo folding pathway of rhodopsin from this laboratory has demonstrated that a variety of site-specific mutations in the P23H, G188R in the intradiscal domain as well as the mutation L125R in the transmembrane helix C, which have been identified in RP, have been shown to cause misfolding of the corresponding opsins. The questions to be asked in the present research proposal are the following: (1) how many of the known RP mutations in rhodopsin actually cause partial or total misfolding and what are their overall consequences in visual transduction; (2) what is the precise chemical nature of the abnormal covalent linkage, a disulfide bond, that characterizes misfolding in RP mutants; and (3) can rearrangement of the wrong disulfide bond to the normal disulfide bond, that characterizes the correctly folded opsin, be achieved in vitro with possible significance in vivo.