Intrinsic disorder and conformational coexistence in auxin coreceptors.
Intrinsic disorder and conformational coexistence in auxin coreceptors.
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生长素共感受器中的内在障碍和构象共存。
DOI：
10.1073/pnas.2221286120
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发表时间：
2023-10-03
影响因子：
11.1
通讯作者：
Kepinski, Stefan
中科院分区：
文献类型：
--
作者：
Ramans-Harborough, Sigurd;Kalverda, Arnout P.;Manfield, Iain W.;Thompson, Gary S.;Kieffer, Martin;Uzunova, Veselina;Quareshy, Mussa;Prusinska, Justyna M.;Roychoudhry, Suruchi;Hayashi, Ken-ichiro;Napier, Richard;del Genio, Charo;Kepinski, Stefan
这篇文章展示了迄今为止标准的AUX/IAA生长素共受体蛋白的最详细和最完整的观点。分子动力学模拟和核磁共振分析表明，虽然AUX/IAA AXR3的N端半部分名义上是无序的，但似乎有采用少量特定构象的倾向。生长素辅助受体的构象共存提供了对地球上植物生命如此关键的蛋白质家族的洞察。生长素/吲哚3-乙酸(AUX/IAA)转录抑制蛋白及其结合的转运蛋白抗性1/生长素信号F盒(TIR1/AFB)是生长素的辅助受体。虽然TIR1的结构已经解决，但负责生长素感知的AUX/IAA蛋白区域的结构特征因其预测的紊乱而变得复杂。在这里，我们使用核磁共振、圆二色谱和分子动力学模拟方法研究了AUX/IAA蛋白IAA17/AXR3的N-末端结构域。我们发现，尽管该区域具有构象灵活性，但AUX/IAA降解子基序核心的关键W-P键在顺式和反式异构体的比例非常高(1：1)，这与顺式构象对形成完全对接的受体复合体的要求一致。我们证明了AXR3的N端一半是多个瞬时结构构象的混合物，在整个系综中有两个主要和不同的构象亚群的倾向。这两个状态与C-端PB1结构域一起建模，以提供AUX/IAA的第一个完整模拟。在生长素存在的情况下，用MD重建每个复合体的组装，两种结构排列都被证明与TIR1受体相结合，模拟得到的接触图与核磁共振信号减少的观察结果非常吻合。总之，我们的结果和方法为探索AUX/IAA辅助受体家族变异的功能意义以及了解内在紊乱在生长素信号转导和其他信号系统中的作用提供了一个平台。
This paper shows the most detailed and complete view to date of a canonical Aux/IAA auxin coreceptor protein. Molecular dynamics simulation, coupled with nuclear magnetic resonance analysis shows that, although nominally disordered, the N-terminal half of the Aux/IAA AXR3 appears to show a propensity toward adoption of a small number of specific conformations. The conformational coexistence in auxin coreceptors provides an insight into a protein family that is so crucial for plant life on earth. AUXIN/INDOLE 3-ACETIC ACID (Aux/IAA) transcriptional repressor proteins and the TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB) proteins to which they bind act as auxin coreceptors. While the structure of TIR1 has been solved, structural characterization of the regions of the Aux/IAA protein responsible for auxin perception has been complicated by their predicted disorder. Here, we use NMR, CD and molecular dynamics simulation to investigate the N-terminal domains of the Aux/IAA protein IAA17/AXR3. We show that despite the conformational flexibility of the region, a critical W–P bond in the core of the Aux/IAA degron motif occurs at a strikingly high (1:1) ratio of cis to trans isomers, consistent with the requirement of the cis conformer for the formation of the fully-docked receptor complex. We show that the N-terminal half of AXR3 is a mixture of multiple transiently structured conformations with a propensity for two predominant and distinct conformational subpopulations within the overall ensemble. These two states were modeled together with the C-terminal PB1 domain to provide the first complete simulation of an Aux/IAA. Using MD to recreate the assembly of each complex in the presence of auxin, both structural arrangements were shown to engage with the TIR1 receptor, and contact maps from the simulations match closely observations of NMR signal-decreases. Together, our results and approach provide a platform for exploring the functional significance of variation in the Aux/IAA coreceptor family and for understanding the role of intrinsic disorder in auxin signal transduction and other signaling systems.
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影响因子：
6.8
作者：
Huang J;MacKerell AD Jr
通讯作者：
MacKerell AD Jr
影响因子：
3.4
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
通讯作者：
Hummer, Gerhard
影响因子：
7.7
作者：
Fendrych, Matyas;Leung, Jeffrey;Friml, Jiri
通讯作者：
Friml, Jiri
影响因子：
4.6
作者：
Guseman, Jessica M.;Hellmuth, Antje;Nemhauser, Jennifer L.
通讯作者：
Nemhauser, Jennifer L.
DOI：
10.1073/pnas.2105819119
发表时间：
2022-03-01
影响因子：
11.1
作者：
Figueiredo MRA;Küpper A;Malone JM;Petrovic T;Figueiredo ABTB;Campagnola G;Peersen OB;Prasad KVSK;Patterson EL;Reddy ASN;Kubeš MF;Napier R;Dayan FE;Preston C;Gaines TA
通讯作者：
Gaines TA