E环半螺旋中螺旋内盐桥的存在会影响AQP1和GlpF通道的转运特性：计算机突变体的分子动力学模拟。,The Journal of Membrane Biology

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E环半螺旋中螺旋内盐桥的存在会影响AQP1和GlpF通道的转运特性：计算机突变体的分子动力学模拟。
The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2018-11-23 , DOI: 10.1007/s00232-018-0054-7
Alok Jain _{1,

2} , Ravi Kumar Verma _{1,

3} , Ramasubbu Sankararamakrishnan ₁

Affiliation

主要内在蛋白（MIP）超家族包含水传输AQP1和甘油特异性GlpF，它们属于两个主要系统发育组，即水通道蛋白（AQP）和水甘油通道蛋白（AQGP）。MIP通道具有六个跨膜螺旋（TM1至TM6）和两个半螺旋（LB和LE）。LE区域为MIP通道内的芳族/精氨酸（Ar / R）选择性过滤器（SF）贡献了两个残基。生物信息学分析表明，所有AQGP在LE半螺旋中均具有螺旋内盐桥（IHSB），并且所有AQGP和大多数AQP在同一区域均具有使Gly和/或Pro不稳定的螺旋。在本文中，我们在计算机上将GlpF中的酸性和碱性残基突变为Ser，并在AQP1 LE半螺旋中引入了盐桥相互作用，方法是在等位上用酸性和碱性残基取代Ser残基。我们使用分子动力学模拟研究了LE半螺旋中IHSB对GlpF和AQP1突变体通道的运输特性的影响。在LE半螺旋中取消了IHSB的情况下，GlpF突变体显示出明显减少的水转运。相反，在两个AQP1突变体中引入IHSB增加了水的运输。LE半螺旋中不存在盐桥会改变SF几何形状，并导致Ar / R选择性过滤器中的溶质具有更高的能垒。LE半螺旋中IHSB的存在与否会影响通道的传输特性，这对于AQGP尤其明显。通过调节其螺旋柔韧性，LE半螺旋也许可以独自或与其他细胞外区域一起在运输中起调节作用。

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Presence of Intra-helical Salt-Bridge in Loop E Half-Helix Can Influence the Transport Properties of AQP1 and GlpF Channels: Molecular Dynamics Simulations of In Silico Mutants.

Major intrinsic protein (MIP) superfamily contains water-transporting AQP1 and glycerol-specific GlpF belonging to two major phylogenetic groups, namely aquaporins (AQPs) and aquaglyceroporins (AQGPs). MIP channels have six transmembrane helices (TM1 to TM6) and two half-helices (LB and LE). LE region contributes two residues to the aromatic/arginine (Ar/R) selectivity filter (SF) within the MIP channel. Bioinformatics analyses have shown that all AQGPs have an intra-helical salt-bridge (IHSB) in LE half-helix and all AQGPs and majority of AQPs have helix destabilizing Gly and/or Pro in the same region. In this paper, we mutated in silico the acidic and basic residues in GlpF to Ser and introduced salt-bridge interaction in AQP1 LE half-helix by substituting Ser residues at the equivalent positions with acidic and basic residues. We investigated the influence of IHSB in LE half-helix on the transport properties of GlpF and AQP1 mutant channels using molecular dynamics simulations. With IHSB abolished in LE half-helix, the GlpF mutant exhibited a significantly reduced water transport. In contrast, the introduction of IHSB in the two AQP1 mutants has increased water transport. Absence of salt-bridge in LE half-helix alters the SF geometry and results in a higher energy barrier for the solutes in the Ar/R selectivity filter. Presence/absence of IHSB in LE half-helix influences the channel transport properties and it is evident especially for the AQGPs. By modulating its helical flexibility, LE half-helix can perhaps play a regulatory role in transport either on its own or in conjunction with other extracellular regions.

更新日期：2019-11-01

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