Mechanisms of Ras membrane organization and signalling: Ras on a rocker.
Mechanisms of Ras membrane organization and signalling: Ras on a rocker.
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DOI：
10.4161/cc.7.17.6596
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发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Hancock JF
中科院分区：
文献类型：
--
作者：
Abankwa D;Gorfe AA;Hancock JF
了解Ras GTP酶的信号传导功能已经成为20多年来许多研究的焦点。Ras的催化结构域和膜锚定C末端高变区（HVR）是其细胞功能所必需的。然而，虽然高度保守的催化结构域已在原子细节的特点，全长膜结合的Ras的结构仍然难以捉摸。缺乏对全长蛋白质的结构知识限制了我们对Ras信号传导的理解。例如，Ras催化结构域与效应子复合物的结构不能为不同Ras亚型的功能特异性提供基础。最近的分子动力学模拟结合生物物理和细胞生物学实验表明，HVR和部分G结构域与脂质尾共同作用，使H-ras锚在质膜上。在GTP结合状态下，H-ras采用允许Ras效应子读出并翻译成相应MAPK信号的取向。在这里，我们讨论的分析，提出了一种新的平衡模型Ras功能的细节。平衡模型合理化Ras膜取向，并可能有助于解释异构体特异性相互作用的Ras与其效应和调制器。
Understanding the signalling function of Ras GTPases has been the focus of much research for over 20 years. Both the catalytic domain and the membrane anchoring C terminal hypervariable region (HVR) of Ras are necessary for its cellular function. However, while the highly conserved catalytic domain has been characterized in atomic detail, the structure of the full-length membrane-bound Ras has remained elusive. Lack of structural knowledge on the full-length protein limited our understanding of Ras signalling. For example, structures of the Ras catalytic domain solved in complex with effectors do not provide a basis for the functional specificity of different Ras isoforms. Recent molecular dynamics simulations in combination with biophysical and cell biological experiments have shown that the HVR and parts of the G domain cofunction with the lipid tails to anchor H-ras to the plasma membrane. In the GTP-bound state, H-ras adopts an orientation that allows read out by Ras effectors and translation into corresponding MAPK signalling. Here we discuss details of an analysis that suggests a novel balance model for Ras functioning. The balance model rationalizes Ras membrane orientation and may help explain isoform specific interactions of Ras with its effectors and modulators.
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影响因子：
21.3
作者：
Prior, IA;Harding, A;Hancock, JF
通讯作者：
Hancock, JF
影响因子：
5.3
作者：
Rotblat, B;Prior, IA;Hancock, JF
通讯作者：
Hancock, JF
影响因子：
7.8
作者：
Prior, Ian A;Muncke, Cornelia;Parton, Robert G;Hancock, John F
通讯作者：
Hancock, John F
影响因子：
5.3
作者：
Rodriguez-Viciana, P;Sabatier, C;McCormick, F
通讯作者：
McCormick, F
影响因子：
3.4
作者：
Kiskowski, Maria A.;Kenworthy, Anne K.
通讯作者：
Kenworthy, Anne K.