SIGNAL TRANSDUCTION COMPLEXES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们想要确定视觉效应酶PDE6本身的结构 与其激活的G蛋白、转导蛋白形成复合体。环核苷酸 磷酸二酯酶(PDE)是信号转导途径的关键调节成分， 是当前药物和正在开发的药物的主要靶点。没有结构是 可用于任何全长的PDE同工酶，尽管有一些用于分离的结构域。 视觉G蛋白级联反应中的关键效应酶是cGMP特异的PDE6，基因 导致人类和动物失明的缺陷。它是一个200 kDa的 杂四聚体(PDE6)。它是一种脂化的外周膜蛋白，形成一种 具有活化G蛋白的脂类依赖复合体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We would like to determine the structure of the effector enzyme of vision, PDE6, by itself and in complex with its activating G-protein, transducin. Cyclic nucleotide phosphodiesterases, PDEs, are key regulatory components of signal transduction pathways, and are major targets of current drugs and those in development. No structures are available for any full-length PDE isozymes, although there are some for isolated domains. The key effector enzyme in the G protein cascade of vision is the cGMP-specific PDE6, genetic deficiencies in which cause blindness in humans and animals. It is a 200 kDa heterotetramer (PDE6¿¿¿¿). It is a lipidated peripheral membrane protein, which forms a lipid-dependent complex with activated G-protein.