A pH-dependent conformational ensemble mediates proton transport through the influenza A/M2 protein.
A pH-dependent conformational ensemble mediates proton transport through the influenza A/M2 protein.
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DOI：
10.1021/bi101229m
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发表时间：
2010-11-30
期刊：
影响因子：
2.9
通讯作者：
DeGrado, William F.
中科院分区：
文献类型：
--
作者：
Polishchuk, Alexei L.;Lear, James D.;Ma, Chunlong;Lamb, Robert A.;Pinto, Lawrence H.;DeGrado, William F.
甲型流感M2蛋白表现出向内整流，pH激活的质子运输饱和，在低pH值。高分辨率的跨膜结构域在高和低pH值的比较表明，pH依赖性的构象变化可能有利于质子传导交替改变的N-末端和C-末端区域的通道作为质子通过跨膜结构域的可及性。在这里，我们表明，M2功能性重组脂质体填充至少三个不同的构象状态在生理相关的pH范围内，与过渡的中点，是一致的，与以前报道的His 37 pKas。然后，我们开发和测试两个类似的，定量的质子运输机制模型，质子化具有不同的质子亲和性和溶剂accessories的结构状态之间的平衡移动。该模型很好地解释了在广泛的pH值和电压范围内的实验数据集的集合，并且仅需要少量的可调参数来准确地描述数据。虽然动力学模型不需要蛋白质的任何特定构象，但它们与基于高分辨率NMR和晶体结构，光谱学和MD计算的大量结构信息一致。
The influenza A M2 protein exhibits inwardly rectifying, pH-activated proton transport that saturates at low pH. A comparison of high-resolution structures of the transmembrane domain at high and low pH suggests that pH-dependent conformational changes may facilitate proton conduction by alternately changing the accessibility of the N-terminal and C-terminal regions of the channel as a proton transits through the transmembrane domain. Here, we show that M2 functionally reconstituted in liposomes populates at least three different conformational states over a physiologically relevant pH range, with transition midpoints that are consistent with previously reported His37 pKas. We then develop and test two similar, quantitative mechanistic models of proton transport, where protonation shifts the equilibrium between structural states having different proton affinities and solvent accessibilities. The models account well for a collection of experimental data sets over a wide range of pHs and voltages and require only a small number of adjustable parameters to accurately describe the data. While the kinetic models do not require any specific conformation for the protein, they nevertheless are consistent with a large body of structural information based on high-resolution NMR and crystallographic structures, optical spectroscopy, and MD calculations.
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影响因子：
2.9
作者：
Nguyen, Phuong A.;Soto, Cinque S.;Polishchuk, Alexei;Caputo, Gregory A.;Tatko, Chad D.;Ma, Chunlong;Ohigashi, Yuki;Pinto, Lawrence H.;DeGrado, William F.;Howard, Kathleen P.
通讯作者：
Howard, Kathleen P.
影响因子：
3.5
作者：
Lear, JD
通讯作者：
Lear, JD
影响因子：
3.7
作者：
GRAMBAS, S;HAY, AJ
通讯作者：
HAY, AJ
影响因子：
3.5
作者：
MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
5
作者：
Czabotar, PE;Martin, SR;Hay, AJ
通讯作者：
Hay, AJ