Structural basis of elongation factor 2 switching.
Structural basis of elongation factor 2 switching.
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DOI：
10.1016/j.crstbi.2020.02.001
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发表时间：
2020
影响因子：
2.8
通讯作者：
Ealick SE
中科院分区：
文献类型：
--
作者：
Fenwick MK;Ealick SE
考古细菌和真核生物伸长因子2(EF-2)和细菌伸长因子G(EF-G)是催化tRNA和mRNA核糖体易位的五种结构域GTP酶。在经典的激活机制中，GTP酶是通过GDP/GTP交换来启动的，这伴随着两个被称为开关I和II的柔性片段的有序。然而，EF-2和EF-G的晶体结构到目前为止还没有揭示出经典机制所需的构象。在这里，我们描述了与GMPPCP(GppCp)和镁结合的甲烷操作菌硝基还原化合物EF-2(MNEF-2)和MNEF-2-H595N的晶体结构，显示出以前未见报道的紧密构象。结构域III与其他四个结构域形成界面，总体构象类似于真核剪接体GTP酶SNU114的构象。GMPPCP的伽马磷酸盐是通过与开关I和P环结构元件相互作用而检测到的。开关II是高度有序的，而开关I显示了可变的有序度。有序状态导致结构域I-III的紧密结构域间排列，并形成涉及P-环和开关I的部分预测的单价阳离子部位。开关II中基本组氨酸残基的侧链被置于延伸因子EF-Tu的“开”状态观察到的非活性构象中。MNEF-2和MNEF-2-H595N的致密构象表明其处于无核糖体的构象状态。结合GTP类似物和镁的无核糖体延伸因子2(EF-2)的晶体结构。紧凑的构象和P-环路、开关I和开关II的结构暗示着“开”状态。结构域I-III的排列类似于核糖体结合的EF-2/EF-G与GTP类似物的络合。Switch II组氨酸在无核糖体的EF-Tu的“开”状态下显示出不活跃的构象。
Archaebacterial and eukaryotic elongation factor 2 (EF-2) and bacterial elongation factor G (EF-G) are five domain GTPases that catalyze the ribosomal translocation of tRNA and mRNA. In the classical mechanism of activation, GTPases are switched on through GDP/GTP exchange, which is accompanied by the ordering of two flexible segments called switch I and II. However, crystal structures of EF-2 and EF-G have thus far not revealed the conformations required by the classical mechanism. Here, we describe crystal structures of Methanoperedens nitroreducens EF-2 (MnEF-2) and MnEF-2-H595N bound to GMPPCP (GppCp) and magnesium displaying previously unreported compact conformations. Domain III forms interfaces with the other four domains and the overall conformations resemble that of SNU114, the eukaryotic spliceosomal GTPase. The gamma phosphate of GMPPCP is detected through interactions with switch I and a P-loop structural element. Switch II is highly ordered whereas switch I shows a variable degree of ordering. The ordered state results in a tight interdomain arrangement of domains I-III and the formation of a portion of a predicted monovalent cation site involving the P-loop and switch I. The side chain of an essential histidine residue in switch II is placed in the inactive conformation observed for the “on” state of elongation factor EF-Tu. The compact conformations of MnEF-2 and MnEF-2-H595N suggest an “on” ribosome-free conformational state. Crystal structures of ribosome-free elongation factor 2 (EF-2) bound to GTP analog and magnesium. Compact conformation and P-loop, switch I, and switch II structures suggest “on” state. Arrangement of domains I-III similar to that of ribosome-bound EF-2/EF-G complexed with GTP analog. Switch II histidine shows inactive conformation observed for “on” state of ribosome-free EF-Tu.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
5.4
作者：
Chen, Yang;Koripella, Ravi Kiran;Selmer, Maria
通讯作者：
Selmer, Maria
DPH2与伸长因子2的复合物中的晶体结构揭示了双胺生物合成的第一步的结构基础。
影响因子：
2.9
作者：
Fenwick MK;Dong M;Lin H;Ealick SE
通讯作者：
Ealick SE
影响因子：
5.7
作者：
KJELDGAARD, M;NISSEN, P;NYBORG, J
通讯作者：
NYBORG, J
影响因子：
11.4
作者：
Fabrizio, P;Laggerbauer, B;Luhrmann, R
通讯作者：
Luhrmann, R