TERTIARY AND QUATERNARY STRUCTURAL-CHANGES IN G(I-ALPHA-1) INDUCED BY GTP HYDROLYSIS
TERTIARY AND QUATERNARY STRUCTURAL-CHANGES IN G(I-ALPHA-1) INDUCED BY GTP HYDROLYSIS
复制标题
DOI：
10.1126/science.270.5238.954
复制
发表时间：
1995-11-10
期刊：
影响因子：
56.9
通讯作者：
SPRANG, SR
中科院分区：
文献类型：
--
作者：
MIXON, MB;LEE, E;SPRANG, SR
2.2埃分辨率的结晶学分析表明，鸟苷三磷酸(GTP)的水解触发了异源三聚体G蛋白α亚基G(Iα1)的构象变化。Switch II和Switch III片段变得无序，连接RAS和α螺旋结构域的连接子II移动，从而改变了潜在效应器和β-伽马结合区的结构。α-螺旋结构域和RAS结构域之间的联系减弱，可能有助于鸟苷二磷酸(GDP)的释放。氨基和羧基末端包含受体和β-伽马结合决定簇，在与GTP的络合物中无序，但在GDP水解时被组织成一个紧凑的微域。氨基末端还与晶格中相邻的阿尔法亚基形成广泛的四元接触，表明阿尔法亚基或杂三聚体的多聚体可能在信号转导中发挥作用。
Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein alpha subunit, G(i alpha 1). The switch II and switch III segments become disordered, and linker II connecting the Ras and alpha helical domains moves, thus altering the structures of potential effector and beta gamma binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and beta gamma binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, suggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction.