LIGHT ACTIVATED RHODOPSIN INDUCES STRUCT BINDING MOTIF IN G PROTEIN ALPHA

一个大的跨膜受体超家族控制细胞 通过催化激活多种细胞外信号， 异源三聚体GTP结合蛋白的特定类型。 如何将这些 受体促进G蛋白a亚基上的核苷酸交换， 启动信号放大是未知。 三维 Gt a亚基C末端十一肽Gta（340-350）的结构 IKENLKDCGLF，通过TRNOE光谱法测定，同时结合到 光激视紫红质 视紫红质的光激活导致 从Gta（340-350）的无序构象到 一个螺旋形的结合基序，后面是一个开放的反向的转折 以Gly 348为中心，是aL型的螺旋终止C-加帽基序。 Gt的NMR结构与GDP结合的X射线结构的对接 揭示了光激发的视紫红质促进了 C-末端终止的残基325-346上的连续螺旋 具有独特关键疏水性侧面簇的螺旋帽 店 一种激活受体控制的分子机制 G蛋白通过受体G的可逆构象变化 蛋白质的界面。

A large superfamily of transmembrane receptors control cellular responses to diverse extracellular signals by catalyzing activation of specific types of heterotrimeric GTP-binding proteins. How these receptors promote nucleotide exchange on G-protein a-subunits to initiate signal amplification is unknown. The three-dimensional structure of the Gt a-subunit C-terminal undecapeptide, Gta(340-350) IKENLKDCGLF, was determined by TRNOE spectroscopy while bound to photoexcited rhodopsin. Light-activation of rhodopsin causes a dramatic shift from a disordered conformation of Gta(340-350) to a binding motif with a helical turn followed by an open reverse turn centered at Gly348, a helix-terminating C-capping motif of an aL-type. Docking of the NMR structure to the GDP-bound X-ray structure of Gt reveals that photoexcited rhodopsin promotes the formation of a continuous helix over residues 325-346 terminated by the C-terminal helical cap with a unique cluster of crucial hydr ophobic si de chains. A molecular mechanism by which activated receptors control G-proteins through reversible conformational changes at the receptor-G protein interface is demonstrated.