The C-terminal region of human eukaryotic elongation factor 1B delta
The C-terminal region of human eukaryotic elongation factor 1B delta
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人真核延伸因子 1B δ 的 C 末端区域
DOI：
10.1007/s10858-016-0012-6
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发表时间：
2016
影响因子：
2.7
通讯作者：
Yingang Feng
中科院分区：
文献类型：
--
作者：
Huiwen Wu;Chen Wang;Weibin Gong;Jinfeng Wang;Jinsong Xuan;Sarah Perrett;Yingang Feng
在真核蛋白生物合成的延伸步骤中，gtp结合活性状态下的真核延伸因子1A （eEF1A）将氨基酸基tRNA （aatRNA）转运到核糖体的A位点（Sasikumar et al. 2012）。正确的密码子-反密码子配对诱导GTP水解为GDP，从而导致eEF1A的构象变化，导致其从核糖体和aa-tRNA中释放。含有2-4个亚基的真核延伸因子1B （eEF1B）复合体有助于将GDP从eEF1A固有的缓慢（* 0.7 9 10-3/s）解离速率提高约3000倍，并导致GTP重新加载和eEF1A再激活（Janssen和Moller 1988）。eEF1B复合体由一个或两个鸟嘌呤核苷酸交换因子（GEFs）组成（EF1Ba存在于所有真核生物中，eEF1Bd仅存在于后生动物中，eEF1Bb仅存在于植物中），一个名为eEF1Bc的支架成分，另外在后生动物中还有一个缬氨酸- trna合成酶（Val-RS） （Le Sourd et al. 2006）。由于没有可用的eEF1B复合物的结构，已经提出了几种模型来解释eEF1B复合物在不同物种中的组装（Janssen et al. 1994; Sheu and Traugh 1997; Mansilla et al. 2002）。eEF1B络合物的GEF是催化成分，每个GEF都包含两个区域（van Damme et al. 1990; Wu et al. 2015）：一个保守程度较低的n端区域（Sanders et al. 1993）和一个高度保守的c端区域，其中包括一个中心酸性区域，称为CAR结构域和一个c端催化GEF结构域。n端区域主要负责与eEF1Bc相互作用，促进eEF1B复合物的组装。在c端区域，GEF结构域是一个必需的催化结构域，而CAR结构域对于交换活性不是必需的。然而，研究发现CAR结构域可以增强交换活性并调节GEF活性（Perez et al. 1998; van Damme et al. 1991）。CAR结构域包含酪蛋白激酶2 （CK2）磷酸化位点（Sheu and Traugh 1997），并被证明与翻译控制肿瘤蛋白（TCTP）相互作用，从而抑制eEF1Bd的核苷酸交换活性（Wu et al. 2015; Cans et al. 2003）。尽管GEF和CAR结构域在eEF1Ba、eEF1Bb和eEF1Bd中是高度保守的，但有证据表明，它们的调控可能会影响到eEF1Ba、eEF1Bb和eEF1Bd
In the elongation step of eukaryotic protein biosynthesis, the eukaryotic elongation factor 1A (eEF1A) in its GTP-bound active state transports the aminoacyl tRNA (aatRNA) to the A site of the ribosome (Sasikumar et al. 2012). Correct codon–anticodon pairing induces hydrolysis of GTP to GDP, which results in a conformational change of eEF1A that causes its release from both the ribosome and aa-tRNA. The eukaryotic elongation factor 1B (eEF1B) complex containing 2–4 subunits helps to enhance the intrinsically slow (* 0.7 9 10-3/s) dissociation rate of GDP from eEF1A by approximately 3000-fold and results in GTP reloading and eEF1A reactivation (Janssen and Moller 1988). The eEF1B complex is comprised of one or two guanine nucleotide exchange factors (GEFs)(EF1Ba exists in all eukaryotes, eEF1Bd exists only in metazoans, and eEF1Bb exists only in plants), a scaffold component named eEF1Bc, and a valine-tRNA synthetase (Val-RS) additionally in metazoans (Le Sourd et al. 2006). Because there is no structure of the eEF1B complex available, several models have been proposed to explain the assembly of the eEF1B complex in different species (Janssen et al. 1994; Sheu and Traugh 1997; Mansilla et al. 2002). The GEFs of the eEF1B complex are the catalytic components and each of them contain two regions (van Damme et al. 1990; Wu et al. 2015): a less conserved N-terminal region (Sanders et al. 1993) and a highly conserved C-terminal region which comprises a central acidic region, termed the CAR domain, and a C-terminal catalytic GEF domain. The N-terminal region is mainly responsible for interacting with eEF1Bc to facilitate assembly of the eEF1B complex. In the C-terminal region, the GEF domain is an essential catalytic domain, while the CAR domain is not essential for the exchange activity. However, it was found that the CAR domain may enhance the exchange activity and regulates the GEF activity (Perez et al. 1998; van Damme et al. 1991). The CAR domain contains the casein kinase 2 (CK2) phosphorylation site (Sheu and Traugh 1997) and has been shown to interact with translationally-controlled tumor protein (TCTP) which inhibits the nucleotide-exchange activity of eEF1Bd (Wu et al. 2015; Cans et al. 2003). Even though the GEF and CAR domains are highly conserved in eEF1Ba, eEF1Bb, and eEF1Bd, evidence suggests that the regulation of their