Serial perturbation of MinK in IKs implies an α-helical transmembrane span traversing the channel corpus
Serial perturbation of MinK in IKs implies an α-helical transmembrane span traversing the channel corpus
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DOI：
10.1529/biophysj.107.109702
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Goldstein, Steve A. N.
中科院分区：
文献类型：
--
作者：
Chen, Haijun;Goldstein, Steve A. N.
I-Ks 通道包含四个成孔 KCNQ1 亚基和两个辅助 MinK 亚基。 MinK 影响表面表达、门控电压依赖性、传导和药理学，以产生心脏天然通道的属性特征。 MinK 跨膜结构域 (TMD) 的结构和位置仍有待详细研究。由于门控分析的扰动已正确推断出成孔亚基中 TMD 的外围位置和 α 螺旋性质，因此该方法在此应用于人类 MinK。 23 个连续位点的色氨酸和天冬酰胺取代产生具有 α 螺旋周期性（残基 44-56）的扰动，随后是交替影响模式（残基 56-63）。跨度范围内的精氨酸取代表明，水溶液中仅有 8 个位点被遮挡（残基 50-57）。我们倾向于采用 α 螺旋的 TMD 模型，跨度的外部部分位于脂质-蛋白质边界，内部部分位于通道语料库内，具有复杂的相互作用。
I-Ks channels contain four pore-forming KCNQ1 subunits and two accessory MinK subunits. MinK influences surface expression, voltage-dependence of gating,conduction, and pharmacology to yield the attributes characteristic of native channels in heart. The structure and location of the MinK transmembrane domain (TMD) remains a matter of scrutiny. As perturbation of gating analysis has correctly inferred the peripheral location and alpha-helical nature of TMDs in pore-forming subunits, the method is applied here to human MinK. Tryptophan and Asparagine substitution at 23 consecutive sites yields perturbation with alpha-helical periodicity ( residues 44-56) followed by an alternating impact pattern ( residues 56-63). Arginine substitution across the span suggests that as few as eight sites are occluded from aqueous solution ( residues 50-57). We favor a TMD model that is alpha-helical with the external portion of the span at a lipid-protein boundary and the inner portion within the channel corpus in complex interactions.