Concerted action of two cation filters in the aquaporin water channel
Concerted action of two cation filters in the aquaporin water channel
复制标题
水通道蛋白水通道中两个阳离子过滤器的协同作用
作者：
Binghua Wu;Christina Steinbronn;Magnus Alsterfjord;T. Zeuthen;E. Beitz
水通道蛋白（AQP）促进了几乎所有细胞膜的水运输，具有几乎完美的特异性和高通量率。同时，质子和阳离子被严格排除，以保持离子跨膜梯度。然而，AQP阳离子过滤器尚未得到实验鉴定。我们报道了三个点突变将水特异性AQP1转变为质子/碱阳离子通道，其水渗透性降低，渗透性顺序为：H+ > K+ >Rb+ >Na+ >Cs+ >Li+。与理论模型相反，我们发现在中心asn - pro - ala （NPA）区域的静电斥力不足以排除质子。只有在孔口处芳香族/精氨酸（ar/R）收缩时才能达到完全的质子排斥。相比之下，碱阳离子被NPA区阻断，但通过ar/R收缩泄漏。漏碱AQPs的表达去极化膜电位和细胞存活受损。我们的研究结果表明，碱-紧性但溶质-非选择性的NPA区域是原始通道的特征，而质子-紧性和溶质-选择性的ar/R收缩变体是AQP超家族后来的适应性。
Aquaporin (AQP) facilitated water transport is common to virtually all cell membranes and is marked by almost perfect specificity and high flux rates. Simultaneously, protons and cations are strictly excluded to maintain ionic transmembrane gradients. Yet, the AQP cation filters have not been identified experimentally. We report that three point mutations turned the water‐specific AQP1 into a proton/alkali cation channel with reduced water permeability and the permeability sequence: H+ ≫K+ >Rb+ >Na+ >Cs+ >Li+. Contrary to theoretical models, we found that electrostatic repulsion at the central asn‐pro‐ala (NPA) region does not suffice to exclude protons. Full proton exclusion is reached only in conjunction with the aromatic/arginine (ar/R) constriction at the pore mouth. In contrast, alkali cations are blocked by the NPA region but leak through the ar/R constriction. Expression of alkali‐leaking AQPs depolarized membrane potentials and compromised cell survival. Our results hint at the alkali‐tight but solute‐unselective NPA region as a feature of primordial channels and the proton‐tight and solute‐selective ar/R constriction variants as later adaptations within the AQP superfamily.
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DOI：
10.1016/s0021-9258(19)37635-5
发表时间：
1988-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
B. Denker;Barbara L. Smith;F. Kuhajda;P. Agre
通讯作者：
B. Denker;Barbara L. Smith;F. Kuhajda;P. Agre
影响因子：
3.4
作者：
Chen, HN;Wu, YJ;Voth, GA
通讯作者：
Voth, GA
影响因子：
2.9
作者：
A. Hoek;Michael C. Wiener;J. Verbavatz;Dennis Brown;Peter H. Lipniunas;Raymond R. Townsend;A. Verkman
通讯作者：
A. Hoek;Michael C. Wiener;J. Verbavatz;Dennis Brown;Peter H. Lipniunas;Raymond R. Townsend;A. Verkman
影响因子：
3.4
作者：
Chen, Hanning;Ilan, Boaz;Voth, Gregory A.
通讯作者：
Voth, Gregory A.