An open-pore structure of the mechanosensitive channel MscL derived by determining transmembrane domain interactions upon gating
An open-pore structure of the mechanosensitive channel MscL derived by determining transmembrane domain interactions upon gating
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DOI：
10.1096/fj.09-129296
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Blount, Paul
中科院分区：
文献类型：
--
作者：
Li, Yuezhou;Wray, Robin;Blount, Paul
机械感觉，检测机械力的能力，是听觉，平衡，触觉和疼痛以及肾脏和心血管调节的基础。虽然传感器被认为是通道，但对真核生物机械敏感通道或其分子机制知之甚少。因此，由于其易处理的性质，作为体内渗透“紧急释放阀”的细菌机械敏感通道MscL已经成为机械敏感通道如何能够感知和响应膜张力的范例。在这里，我们已经确定了门控时发生的MscL跨膜结构域之间的结构重排和相互作用。我们利用静电排斥测试：如果两个残基接近门控，我们预测，在这些网站取代类似的电荷将抑制门控。体内生长和活力以及体外囊泡通量和电生理数据都支持残基G26和I92在门控后直接相互作用的假设。由此产生的模型预测其他相互作用的残基。其中一组V23和I96通过二硫键捕获以及静电排斥测试被证实在门控时真正相互作用。总之，这些数据强烈地表明了MscL门控时发生的结构转变和残基-残基接近的模型。李，Y.，雷河伊顿角，澳-地Blount，P. An open-pore structure of the mechanosensitive channel MscL derived by determining transmembrane domain interactions upon gating. FASEB J. 23，2197-2204（2009）
Mechanosensation, the ability to detect mechanical forces, underlies the senses of hearing, balance, touch, and pain, as well as renal and cardiovascular regulation. Although the sensors are thought to be channels, relatively little is known about eukaryotic mechanosensitive channels or their molecular mechanisms. Thus, because of its tractable nature, a bacterial mechanosensitive channel that serves as an in vivo osmotic "emergency release valve," MscL, has become a paradigm of how a mechanosensitive channel can sense and respond to membrane tension. Here, we have determined the structural rearrangements and interactions between transmembrane domains of MscL that occur upon gating. We utilize an electrostatic repulsion test: If two residues approach upon gating we predicted that substituting like-charges at those sites would inhibit gating. The in vivo growth and viability and in vitro vesicular flux and electrophysiological data all support the hypothesis that residues G26 and I92 directly interact upon gating. The resulting model predicted other interacting residues. One of these sets, V23 and I96, was confirmed to truly interact upon gating by disulfide trapping as well as the electrostatic repulsion test. Together, the data strongly suggest a model for structural transitions and residue-residue proximities that occur upon MscL gating.-Li, Y., Wray, R., Eaton, C., Blount, P. An open-pore structure of the mechanosensitive channel MscL derived by determining transmembrane domain interactions upon gating. FASEB J. 23, 2197-2204 (2009)