Differential lipid dependence of the function of bacterial sodium channels.
Differential lipid dependence of the function of bacterial sodium channels.
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细菌钠通道功能的差异脂质依赖性。
DOI：
10.1371/journal.pone.0061216
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wallace BA
中科院分区：
文献类型：
--
作者：
D'Avanzo N;McCusker EC;Powl AM;Miles AJ;Nichols CG;Wallace BA
脂质双层对于维持细胞区室的完整性非常重要，并且在提供膜蛋白结构、构象灵活性和功能所需的疏水性和带电相互作用方面发挥着至关重要的作用。为了直接评估电压门控钠通道活性的脂质依赖性，我们通过将 22Na+ 累积摄取到含有 3:1 比例的 1-棕榈酰 2-油酰磷脂酰乙醇胺和不同“客体”甘油磷脂的蛋白脂质体中，比较了三种细菌钠通道同源物（NaChBac、NavMs 和 NavSp）的活性。我们观察到每个测试通道都有独特的脂质谱。 NavMs 和 NavSp 对不同的带负电荷的脂质（分别是磷脂酰肌醇和磷脂酰甘油）表现出强烈的偏好，而 NaChBac 则表现出随脂质类型变化较小的变化。为了研究这些差异的分子基础，我们使用同步辐射圆二色光谱来比较不同成分的脂质体的结构，并使用分子建模和静电计算来合理化所看到的功能差异。然后，我们检查了仅孔的结构（去除了电压传感器子域），发现在这些通道中，脂质特异性大大降低，这表明特定脂质对电压门控钠通道的影响主要来自于它们与电压传感子域相互作用的能力。
The lipid bilayer is important for maintaining the integrity of cellular compartments and plays a vital role in providing the hydrophobic and charged interactions necessary for membrane protein structure, conformational flexibility and function. To directly assess the lipid dependence of activity for voltage-gated sodium channels, we compared the activity of three bacterial sodium channel homologues (NaChBac, NavMs, and NavSp) by cumulative 22Na+ uptake into proteoliposomes containing a 3∶1 ratio of 1-palmitoyl 2-oleoyl phosphatidylethanolamine and different “guest” glycerophospholipids. We observed a unique lipid profile for each channel tested. NavMs and NavSp showed strong preference for different negatively-charged lipids (phosphatidylinositol and phosphatidylglycerol, respectively), whilst NaChBac exhibited a more modest variation with lipid type. To investigate the molecular bases of these differences we used synchrotron radiation circular dichroism spectroscopy to compare structures in liposomes of different composition, and molecular modeling and electrostatics calculations to rationalize the functional differences seen. We then examined pore-only constructs (with voltage sensor subdomains removed) and found that in these channels the lipid specificity was drastically reduced, suggesting that the specific lipid influences on voltage-gated sodium channels arise primarily from their abilities to interact with the voltage-sensing subdomains.
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影响因子：
3.7
作者：
D'Avanzo N;Hyrc K;Enkvetchakul D;Covey DF;Nichols CG
通讯作者：
Nichols CG
影响因子：
64.8
作者：
Payandeh, Jian;El-Din, Tamer M. Gamal;Scheuer, Todd;Zheng, Ning;Catterall, William A.
通讯作者：
Catterall, William A.
影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
3.8
作者：
Lundbaek, Jens A;Birn, Pia;Hansen, Anker J;Sogaard, Rikke;Nielsen, Claus;Girshman, Jeffrey;Bruno, Michael J;Tape, Sonya E;Egebjerg, Jan;Greathouse, Denise V;Mattice, Gwendolyn L;Koeppe, Roger E 2nd;Andersen, Olaf S
通讯作者：
Andersen, Olaf S
影响因子：
2.9
作者：
Nurani, Ghasem;Radford, Matthew;Wallace, B. A.
通讯作者：
Wallace, B. A.