Thermo TRP channels as modular proteins with allosteric gating
Thermo TRP channels as modular proteins with allosteric gating
复制标题
DOI：
10.1016/j.ceca.2007.04.004
复制
发表时间：
2007-10-01
期刊：
影响因子：
4
通讯作者：
Vargas, Guillermo
中科院分区：
文献类型：
--
作者：
Latorre, Ramon;Brauchi, Sebastian;Vargas, Guillermo
离子通道通过感知刺激物（如膜电压、配体结合或温度）激活，并将此信息转化为打开通道孔的构象变化。因此，理解离子通道功能的一个关键问题是参与感知刺激（传感器）和打开孔（门）的蛋白质结构域如何进行通信。在这方面，瞬时受体电位（TRP）通道赋予温度感觉[A.达卡，V. Viswanath，A. Patapoutian，TRP离子通道和温度感觉，Annu。神经科学评论29（2006）135-161; I.S. Ramsey，M. Delling，D.E. Clapham，TRP通道介绍，Annu。Rev.Physiol.68（2006）619-647]（thermoTRP; Q（10）> 10）在它们整合各种物理和化学刺激的程度上是独特的。在一些情况下，例如香草素受体TRPV 1 [M. J. Caterina，M.A. Schumacher，M. Tominaga，T.A.罗森莱文，D. Julius，The capsaicin receptor：a heat-activated ion channel in the pain pathway，Nature 389（1997）816-824]和TRPAI [G.M. Story，A.M. Peier，A.J. Reeve，S.R. Eid，J. Mosbacher，T.R. Hricik，T. J.厄利，A.C.放大图片作者：Hergarden，D.A. Andersson，S. W. Hwang，P. McIntyre，T. Jegla，S. Bevan，A. Patapoutian，ANKTM 1，一种在伤害感受神经元中表达的TRP样通道，被低温激活，Cell 112（2003）819-829; S. Jordt，D. Julius，Molecular basis for species-specific sensitivity to“hot”chili peppers，Cell 108（2002）421-430]这些刺激的整合引起疼痛[M. Tominaga，M.J. Caterina，A.B. Malmberg，T.A.罗森，H.吉尔伯特，K.斯金纳，B.E. A.I. Raumann Basbaum，D. Julius，克隆辣椒素受体整合多种产生疼痛的刺激，Neuron 21（1998）531-543; M. Bandell，A. Dubin，M. Petrus，A. Orth，J. Mathur，S. Hwang，A.黄氏A. Patapoutian，High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol，Nat. Neurosci. 9（2006）466-468; S.奥尔堡，B。Yurgionas，JA.吉拉岛卡斯帕尼Heppenstall，Direct activation of the ion channel TRPA1 by Ca2+，Nat. Neurosci. 10（2007）277-279]。这些刺激包括电压、pH、激动剂结合和温度。了解这些不同的生理信号中的每一个如何调节通道开放，将有助于了解可以独立或协同作用以影响通道激活的机械联系。在本文中，我们表明热TRP通道形成蛋白是模块化的，因为某些结构或结构（模块）赋予温度依赖性调节，而其他结构赋予电压依赖性调节。我们还讨论了热激活和冷激活的热力学基础，以阐明是什么赋予这些通道直接通过温度门控的能力。(c)2007爱思唯尔有限公司保留所有权利。
Ion channels activate by sensing stimuli such as membrane voltage, ligand binding or temperature and transduce this information into conformational changes that open the channel pore. Thus, a key question in understanding ion channel function is how do the protein domains involved in sensing stimuli (sensors) and opening the pore (gates) communicate. In this regard, transient receptor potential (TRP) channels that confer thermosensation [A. Dhaka, V. Viswanath, A. Patapoutian, TRP ion channels and temperature sensation, Annu. Rev. Neurosci. 29 (2006) 135-161; I.S. Ramsey, M. Delling, D.E. Clapham, An introduction to TRP channels, Annu. Rev. Physiol. 68 (2006) 619-647] (thermoTRP; Q(10) > 10) are unique to the extent that they integrate a variety of physical and chemical stimuli. In some cases such as, for example, the vanilloid receptor TRPV1 [M.J. Caterina, M.A. Schumacher, M. Tominaga, T.A. Rosen, J.D. Levine, D. Julius, The capsaicin receptor: a heat-activated ion channel in the pain pathway, Nature 389 (1997) 816-824] and TRPAI [G.M. Story, A.M. Peier, A.J. Reeve, S.R. Eid, J. Mosbacher, T.R. Hricik, T.J. Earley, A.C. Hergarden, D.A. Andersson, S.W. Hwang, P. McIntyre, T. Jegla, S. Bevan, A. Patapoutian, ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures, Cell 112 (2003) 819-829; S. Jordt, D. Julius, Molecular basis for species-specific sensitivity to "hot" chilli peppers, Cell 108 (2002) 421-430] the integration of these stimuli elicit pain [M. Tominaga, M.J. Caterina, A.B. Malmberg, T.A. Rosen, H. Gilbert, K. Skinner, B.E. Raumann, A.I. Basbaum, D. Julius, The cloned capsaicin receptor integrates multiple pain-producing stimuli, Neuron 21 (1998) 531-543; M. Bandell, A. Dubin, M. Petrus, A. Orth, J. Mathur, S. Hwang, A. Patapoutian, High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol, Nat. Neurosci. 9 (2006) 466-468; S. Zurborg, B. Yurgionas, JA. Jira, O. Caspani, P.A. Heppenstall, Direct activation of the ion channel TRPA1 by Ca2+, Nat. Neurosci. 10 (2007) 277-279]. These stimuli include voltage, pH, agonist binding, and temperature. Understanding how each of these distinct physiological signals regulate channel opening will be informative about the mechanical linkages that can act either independently or in concert to influence channel activation. In this paper we show that thermoTRP channel-forming proteins are modular in the sense that certain structure or structures (modules) confer temperature-dependent regulation, whereas others confer voltage-dependent regulation. We also discuss the thermodynamic basis of heat and cold activation in an effort to elucidate what confer to these channels the capability to be gated by temperature directly. (c) 2007 Elsevier Ltd. All rights reserved.