CRYSTAL-STRUCTURE OF AN ACTIVE FORM OF RAS PROTEIN, A COMPLEX OF A GTP ANALOG AND THE HRAS P21 CATALYTIC DOMAIN
CRYSTAL-STRUCTURE OF AN ACTIVE FORM OF RAS PROTEIN, A COMPLEX OF A GTP ANALOG AND THE HRAS P21 CATALYTIC DOMAIN
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DOI：
10.1073/pnas.87.12.4849
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
KIM, SH
中科院分区：
文献类型：
--
作者：
BRUNGER, AT;MILBURN, MV;KIM, SH
正常RAS蛋白在生长信号从细胞外空间到细胞内空间的转导中发挥分子开关的关键作用。当 GTP 结合时开关状态为“打开”，当 GDP 与蛋白质结合时开关状态为“关闭”。不可水解的 GTP 类似物和 RAS 蛋白催化结构域之间的复合物的晶体结构已通过旋转翻译搜索方法确定。在搜索中使用单个分子作为探针确定了四个独立分子的方向和位置。晶体结构表明，GTP 类似物的 γ 磷酸盐在蛋白质的两个环区域上诱导广泛的构象变化。
Normal RAS proteins play a key role of molecular switch in the transduction of the growth signal from extracellular to intracellular space. The state of the switch is "on" when GTP is bound and "off" when GDP is bound to the protein. The crystal structure of a complex between a nonhydrolyzable GTP analog and the catalytic domain of a RAS protein has been determined by a rotation-translation search method. The orientations and positions of four independent molecules have been determined using a single molecule as a probe in the search. The crystal structure reveals that the gamma phosphate of the GTP analog induces extensive conformational changes on two loop regions of the protein.