Structural dynamics of an isolated voltage-sensor domain in a lipid bilayer
Structural dynamics of an isolated voltage-sensor domain in a lipid bilayer
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DOI：
10.1016/j.str.2007.12.015
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Perozo, Eduardo
中科院分区：
文献类型：
--
作者：
Chakrapani, Sudha;Cuello, Luis G.;Perozo, Eduardo
电压传感器域（VSD）和孔域（PD）之间的强相互作用是电压门控通道功能的基础。在一些电压敏感蛋白中，VSD已被证明在没有典型PD的情况下起作用，尽管其结构和寡聚状态仍然未知。在这里，使用EPR光谱，我们表明，孤立的VSD的KvAP可以保持单体在重建的双层，并保留跨膜构象。我们发现，充满水的裂缝延伸到周围的膜S3，有利于质子/阳离子的运输支架，是固有的VSD。与全长KvAP相比，溶剂可及性的差异使我们能够定义PD在VSD上的相互作用足迹。这种相互作用以S1和S2为中心，并表明相对于Kv1.2-Kv2.1嵌合体旋转70度-100度。KV通道、HV通道和电压敏感性磷酸酶的序列保守模式揭示了几个近乎普遍的特征，表明所有VSD具有共同的分子结构。
A strong interplay between the voltage-sensor domain (VSD) and the pore domain (PD) underlies voltage-gated channel functions. In a few voltage-sensitive proteins, the VSD has been shown to function without a canonical PD, although its structure and oligomeric state remain unknown. Here, using EPR spectroscopy, we show that the isolated VSD of KvAP can remain monomeric in a reconstituted bilayer and retain a transmembrane conformation. We find that water-filled crevices extending deep into the membrane around S3, a scaffold conducive to transport of protons/cations, are intrinsic to the VSD. Differences in solvent accessibility in comparison to the full-length KvAP allowed us to define an interacting footprint of the PD on the VSD. This interaction is centered around S1 and S2 and suggests a rotation of 70 degrees-100 degrees relative to Kvl.2-Kv2.1 chimera. Sequence-conservation patterns in Kv channels, Hv channels, and voltage-sensitive phosphatases reveal several near-universal features suggesting a common molecular architecture for all VSDs.