The inhibitory helix controls the intramolecular conformational switching of the C-terminus of STIM1.
The inhibitory helix controls the intramolecular conformational switching of the C-terminus of STIM1.
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抑制性螺旋控制 STIM1 C 末端的分子内构象转换
DOI：
10.1371/journal.pone.0074735
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Cui B;Yang X;Li S;Lin Z;Wang Z;Dong C;Shen Y
钙池操纵的钙内流（SOCE）是许多细胞类型中重要的钙信号通路。在感应到内质网（ER）腔中的Ca 2+储存耗尽后，STIM 1（STromal Interaction Molecule 1）寡聚化，然后与Orai 1钙通道相互作用并激活Orai 1钙通道。我们前期的研究表明，STIM 1的第一个卷曲螺旋区（CC 1）附近的抑制性螺旋（IH）可以使STIM 1的整个C端处于失活状态。然而，CC 1-IH驱动STIM 1从静息状态转变为活性状态的特定构象变化仍然难以捉摸。在此，我们报告的CC 1-IH的结构分析，这表明，整个CC 1-IH分子形成一个很长的螺旋。结构和生化分析表明，IH，而不是CC 1区，有助于STIM 1的寡聚化。小角X射线散射（SAXS）分析表明，包括IH区域的STIM 1的C-末端显示出塌陷的构象，而没有IH区域的构建体具有延伸的构象。这两种构象可能对应于激活前后STIM 1的C-末端的构象状态。两者合计，我们的研究结果提供了直接的生化证据表明，IH区域控制STIM 1的C-末端的构象转换。
Store-operated Ca2+ entry (SOCE) is a critical Ca2+ signaling pathway in many cell types. After sensing Ca2+ store depletion in the endoplasmic reticulum (ER) lumen, STIM1 (STromal Interaction Molecule 1) oligomerizes and then interacts with and activates the Orai1 calcium channel. Our previous research has demonstrated that the inhibitory helix (IH) adjacent to the first coiled-coil region (CC1) of STIM1 may keep the whole C-terminus of STIM1 in an inactive state. However, the specific conformational change of CC1-IH that drives the transition of STIM1 from the resting state to the active state remains elusive. Herein, we report the structural analysis of CC1-IH, which revealed that the entire CC1-IH molecule forms a very long helix. Structural and biochemical analyses indicated that IH, and not the CC1 region, contributes to the oligomerization of STIM1. Small-angle X-ray scattering (SAXS) analysis suggested that the C-terminus of STIM1 including the IH region displays a collapsed conformation, whereas the construct without the IH region has an extended conformation. These two conformations may correspond to the conformational states of the C-terminus of STIM1 before and after activation. Taken together, our results provide direct biochemical evidence that the IH region controls the conformational switching of the C-terminus of STIM1.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.6
作者：
LEE, B;RICHARDS, FM
通讯作者：
RICHARDS, FM
影响因子：
64.8
作者：
Prakriya, Murali;Feske, Stefan;Hogan, Patrick G.
通讯作者：
Hogan, Patrick G.
影响因子：
3.4
作者：
Schuck, P
通讯作者：
Schuck, P
影响因子：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI