Gating and conductance changes in BK Ca channels in bilayers are reciprocal
Gating and conductance changes in BK Ca channels in bilayers are reciprocal
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DOI：
10.1007/s00232-006-0034-1
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发表时间：
2006-09-01
影响因子：
2.4
通讯作者：
Treistman, Steven N.
中科院分区：
文献类型：
--
作者：
Connell, Robert J. O.;Yuan, Chunbo;Treistman, Steven N.
与脂质双层的烃部分和跨膜蛋白的疏水区域之间的错配相关的能量需要一个或两个组分变形以试图使能量差最小化。跨膜钾通道亚基由不同的结构基序组成，每个结构基序负责离子选择性、电导和门控能力。每一种都具有与其氨基酸组成相称的固有灵活性。然而，我们并不清楚，每一个结构性的主题将如何对施加在整个结构上的固定量的扭曲做出反应。我们检测了插入含有1，2-二油酰-3-磷脂酰乙醇胺（DOPE）或DOPE与1，2-二油酰-sn-甘油基-3-磷酸胆碱（DOPC）或鞘磷脂（SPM）和1-棕榈酰-2-油酰-3-磷脂酰乙醇胺（POPE）的平面脂质双层中的单个BKCa通道（hKCa α亚基）的单通道电导（G（c））和门控（开放概率，P-o）。这后三个二元混合物形成了稳定的膜，由原子力显微镜测定的厚度域的不同分布。放置在每个组合中的通道应暴露于不同的失真量。被迫进入DOPE/SPM双层含有两种不同厚度的脂质结构域的BKCa通道显示出两种不同的Gc和Po水平。Gc和Po的变化是相互的。较大的电导伴随着较小的门控值，反之亦然。通道被迫进入含有不同厚度的脂质结构域的POPE/SPM双层显示出两个以上的不同水平的GC和PO。通道放置在一个统一的双层（DOPE/DOPC）显示出均匀分布的电导和激活。我们的结论是，这两个通道的功能是本地化的通道的内部和外部域响应变形和固定量的失真的结果在蛋白质功能的相互变化。
The energy associated with a mismatch between the hydrocarbon portions of a lipid bilayer and the hydrophobic regions of a transmembrane protein requires that one or both components deform in an attempt to minimize the energy difference. Transmembrane potassium channel subunits are composed of different structural motifs, each responsible for ion-selectivity, conductance and gating capabilities. Each has an inherent degree of flexibility commensurate with its amino acid composition. It is not clear, however, how each structural motif will respond to a fixed amount of distortion applied to the whole structure. We examined the single-channel conductance (G(c)) and gating (open probability, P-o) of single BKCa channels (hslo alpha-subunits) inserted into planar lipid bilayers containing 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE) or DOPE with either 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or sphingomyelin (SPM) and 1-palmitoyl-2-oleoyl-3-phosphatidylethanolamine (POPE) with SPM. These latter three binary mixtures formed stable membranes with different distributions of thickness domains as determined by atomic force microscopy. Channels placed in each composition should be exposed to different amounts of distortion. BKCa channels forced into the DOPE/SPM bilayer containing lipid domains with two different thicknesses showed two distinct levels of Gc and Po. The alterations in Gc and Po were reciprocal. A larger conductance was accompanied by a smaller value for gating and vice versa. Channels forced into the POPE/SPM bilayer containing lipid domains with different thicknesses showed more than two distinct levels of Gc and Po. Channels placed in a uniform bilayer (DOPE/DOPC) showed a uniform distribution of conductance and activation. We conclude that both the inner and outer domains of the channel where these two channel functions are localized respond to deformation and that a fixed amount of distortion results in reciprocal changes in protein function.