Structure of a GDP:AlF4 complex of the SRP GTPases Ffh and FtsY, and identification of peripheral nucleotide interaction site
Structure of a GDP:AlF4 complex of the SRP GTPases Ffh and FtsY, and identification of peripheral nucleotide interaction site
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DOI：
10.1016/j.jmb.2006.05.031
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发表时间：
2006-07-14
影响因子：
5.6
通讯作者：
Freymann, Douglas M.
中科院分区：
文献类型：
--
作者：
Focia, Pamela J.;Gawronski-Salerno, Joseph;Freymann, Douglas M.
信号识别颗粒（SRP）GTP酶Ffh和FtsY在蛋白质的共翻译靶向中起核心作用，以GTP依赖性方式组装以在膜上产生SRP靶向复合物。已经鉴定了FtsY中的一组残基，其对于伴随脱离的GTP水解是必需的。我们以前曾在结构上论证过，该区域介导的相互作用有助于激活复合体的脱离，并将其称为激活区。我们在这里报告的结构复杂的SRP GTP酶的GDP：AlF4的存在下形成的。该复合物容纳假定的过渡态类似物，而不经历从在GTP类似物GMPPCP存在下形成的基态复合物的结构的显著变化。然而，在共用催化室内确实发生的小的移位可能在功能上是重要的。值得注意的是，一个外部的核苷酸相互作用的网站被确定在激活区域，揭示了一个意想不到的污染GMP分子结合附近的催化室。该位点表现出保守的序列和结构特征，表明与RNA的直接相互作用在调节SRP靶向复合物的活性方面发挥着作用。(c)2006爱思唯尔有限公司保留所有权利。
The signal recognition particle (SRP) GTPases Ffh and FtsY play a central role in co-translational targeting of proteins, assembling in a GTP-dependent manner to generate the SRP targeting complex at the membrane. A suite of residues in FtsY have been identified that are essential for the hydrolysis of GTP that accompanies disengagement. We have argued previously on structural grounds that this region mediates interactions that serve to activate the complex for disengagement and term it the activation region. We report here the structure of a complex of the SRP GTPases formed in the presence of GDP:AlF4. This complex accommodates the putative transition-state analog without undergoing significant change from the structure of the ground-state complex formed in the presence of the GTP analog GMPPCP. However, small shifts that do occur within the shared catalytic chamber may be functionally important. Remarkably, an external nucleotide interaction site was identified at the activation region, revealed by an unexpected contaminating GMP molecule bound adjacent to the catalytic chamber. This site exhibits conserved sequence and structural features that suggest a direct interaction with RNA plays a role in regulating the activity of the SRP targeting complex. (c) 2006 Elsevier Ltd. All rights reserved.