Mechanisms of molecular transport through the urea channel of Helicobacter pylori.
Mechanisms of molecular transport through the urea channel of Helicobacter pylori.
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幽门螺杆菌尿素通道的分子转运机制
DOI：
10.1038/ncomms3900
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发表时间：
2013
影响因子：
16.6
通讯作者：
Ulmschneider, Martin B.
中科院分区：
文献类型：
--
作者：
McNulty, Reginald;Ulmschneider, Jakob P.;Luecke, Hartmut;Ulmschneider, Martin B.
幽门螺杆菌在酸性环境中的生存依赖于胃尿素水解成氨和二氧化碳的细胞质，这可以缓冲病原体的周围质。HpUreI是一种质子门控的内膜通道蛋白，对幽门螺杆菌的胃存活至关重要。HpUreI的晶体结构描述了通道的静态快照，在双层中心附近有两个收缩点，它们太窄，不能让尿素甚至水通过。在这里，我们描述了尿素在原子分辨率上的传输机制，通过不受限制的微秒平衡分子动力学模拟揭示了六聚体通道组装。两个连续的收缩打开以允许尿素的传导，尿素通过决定质子排斥和溶质选择性的保守残基之间的相互作用引导通过通道。值得注意的是，HpUreI以与水通道蛋白相当的速率传导水，这可能是在小浓度梯度下有效运输尿素所必需的。幽门螺杆菌在胃的酸性环境中生存，通过吸收尿素并将其转化为氨和二氧化碳，以缓冲细菌的周围质。通过分子动力学模拟，McNulty等人提供了通过幽门螺杆菌尿素转运体摄取尿素的机制。
Helicobacter pylori survival in acidic environments relies on cytoplasmic hydrolysis of gastric urea into ammonia and carbon dioxide, which buffer the pathogen’s periplasm. Urea uptake is greatly enhanced and regulated by HpUreI, a proton-gated inner membrane channel protein essential for gastric survival of H. pylori. The crystal structure of HpUreI describes a static snapshot of the channel with two constriction sites near the center of the bilayer that are too narrow to allow passage of urea or even water. Here we describe the urea transport mechanism at atomic resolution, revealed by unrestrained microsecond equilibrium molecular dynamics simulations of the hexameric channel assembly. Two consecutive constrictions open to allow conduction of urea, which is guided through the channel by interplay between conserved residues that determine proton rejection and solute selectivity. Remarkably, HpUreI conducts water at rates equivalent to aquaporins, which might be essential for efficient transport of urea at small concentration gradients. Helicobacter pylori survives in the acidic environment of the stomach by taking up urea and converting it to ammonia and carbon dioxide, which buffer the bacterial periplasm. Using molecular dynamics simulations, McNulty et al. provide insight into the mechanism of urea uptake through the H. pylori urea transporter.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
DOI：
10.1073/pnas.0507225103
发表时间：
2006-01-10
影响因子：
11.1
作者：
Beitz, E;Wu, BH;Zeuthen, T
通讯作者：
Zeuthen, T
影响因子：
3.4
作者：
Chen, HN;Wu, YJ;Voth, GA
通讯作者：
Voth, GA
DOI：
10.1038/88563
发表时间：
2001-06-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Ha, NC;Oh, ST;Oh, BH
通讯作者：
Oh, BH
影响因子：
56.9
作者：
de Groot, BL;Grubmüller, H
通讯作者：
Grubmüller, H