Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling.
Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling.
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DOI：
10.1016/j.jmb.2012.12.011
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发表时间：
2013-03-11
影响因子：
5.6
通讯作者：
Crane, Brian R.
中科院分区：
文献类型：
--
作者：
Airola, Michael V.;Huh, Doowon;Sukomon, Nattakan;Widom, Joanne;Sircar, Ria;Borbat, Peter P.;Freed, Jack H.;Watts, Kylie J.;Crane, Brian R.
关键词：
细菌受体通常包含具有不同功能结构域的模块结构，所述功能结构域联合收割机响应刺激而发送信号。虽然在许多情况下已经研究了单个组件的特性，但关于不同模块如何在全长受体中一起工作的信息很少。在这里，我们调查的架构Aer 2，可溶性气敏受体，已成为PAS和聚HAMP结构域信号的模型。与之前确定的氰化物结合状态相比，铁离子、无配体形式的血红素结合PAS结构域的晶体结构识别了配体结合诱导的构象变化，这些变化可能对信号传导机制至关重要。血红素口袋交替与基于血红素的PAS传感器FixL和EcDOS有一些相似之处，但以预测改变PAS-PAS缔合和全长Aer 2内下游HAMP连接的方式传播到Iβ链。PAS和聚HAMP结构域片段的SAXS的复杂性增加允许明确的域分配，并揭示了线性四级结构。Aer 2 PAS的二聚体晶体结构适合以及ab initioSAXS分子信封和脉冲偶极ESR测量PAS间的距离证实了结晶PAS排列Aer 2内。光谱和下拉分析未能检测PAS和HAMP结构域之间的直接相互作用。总体而言，Aer 2信号传导机制不同于E. Coliaer范例，其中侧面PAS-HAMP接触是关键。我们提出了一个在线模型Aer 2信号，其中配体结合诱导PAS结构域结构和亚基协会的改变，通过多HAMP连接中继到下游结构域。
Bacterial receptors typically contain modular architectures with distinct functional domains that combine to send signals in response to stimuli. Although the properties of individual components have been investigated in many contexts, there is little information about how diverse sets of modules work together in full-length receptors. Here we investigate the architecture of Aer2, a soluble gas-sensing receptor that has emerged as a model for PAS and poly-HAMP domain signaling. The crystal structure of the heme-binding PAS domain in the ferric, ligand-free form, in comparison to the previously determined cyanide-bound state, identifies conformational changes induced by ligand binding that are likely essential for the signaling mechanism. Heme-pocket alternations share some similarities with the heme-based PAS sensors FixL and EcDOS, but propagate to the Iβ-strand in a manner predicted to alter PAS-PAS associations and the downstream HAMP junction within full-length Aer2. SAXS of PAS and poly-HAMP domain fragments of increasing complexity allow unambiguous domain assignments and reveal a linear quaternary structure. The Aer2 PAS dimeric crystal structure fits well within ab initioSAXS molecular envelopes and pulsed-dipolar ESR measurements of inter-PAS distances confirm the crystallographic PAS arrangement within Aer2. Spectroscopic and pull-down assays fail to detect direct interactions between the PAS and HAMP domains. Overall, the Aer2 signaling mechanism differs from the E. coliAer paradigm, where side-on PAS-HAMP contacts are key. We propose an in-line model for Aer2 signaling, where ligand binding induces alterations in PAS domain structure and subunit association that is relayed through the poly-HAMP junction to downstream domains.
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影响因子：
5.6
作者：
Miyatake, H;Mukai, M;Shiro, Y
通讯作者：
Shiro, Y
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：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI
影响因子：
3.2
作者：
Herrmann, S;Ma, QH;Taylor, BL
通讯作者：
Taylor, BL
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH