Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine.

Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine.
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DOI:
10.1172/jci0215851
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发表时间:
2002-06
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
D. Kozono;M. Yasui;L. King;P. Agre
D. Kozono;M. Yasui;L. King;P. Agre
中科院分区:
其他
文献类型:
--
作者:
D. Kozono;M. Yasui;L. King;P. Agre

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水穿过细胞膜的运动是生命的基础。水大约占大多数生物体质量的70%,因此需要水的有序分布来维持不同解剖隔室内的适当流体平衡。虽然已知水通过脂质双层扩散,但对于许多生理过程来说,扩散不够快。为了满足这些需求,膜通道蛋白家族进化为快速运输水穿过生物膜。这些蛋白质被称为“水通道蛋白”,存在于所有生命形式中,包括古细菌、真细菌、真菌、植物和所有动物门。自从10年前发现水通道蛋白以来,世界各地的研究人员一直试图了解这些蛋白质的工作原理。选择性、渗透速率和门控机制是表征通道蛋白的三个性质。水通道蛋白对水的运输有很高的选择性,甚至排斥水合氢离子(H3O+)。哺乳动物肾小管的正常功能强调了后者的重要性,肾小管从肾小球滤液中重吸收99%的水,同时由闰细胞分泌酸。水通道蛋白超家族的一些成员被各种小的中性溶质渗透,例如甘油或尿素(称为“水甘油通道蛋白”)(2)。水或甘油通过水通道蛋白的运输代表由渗透或浓度梯度驱动的易化扩散。
The movement of water across cell membranes is fundamental to life. Water constitutes roughly 70% of the mass of most living organisms, so the orderly distribution of water is required to maintain proper fluid balance within different anatomic compartments. Although water is known to diffuse through lipid bilayers, diffusion is not sufficiently rapid for many physiological processes. To accommodate these needs, a family of membrane channel proteins evolved for rapid transport of water across biological membranes. These proteins, termed “aquaporins,” are found in all life forms, including archaea, eubacteria, fungi, plants, and all phyla of animals. Since the discovery of the aquaporins ten years ago (1), researchers around the world have sought to learn how these proteins work. Selectivity, rates of permeation, and gating mechanisms are three properties that characterize channel proteins. Aquaporins are exquisitely selective for the transport of water — even repelling hydronium ions (H3O+). The importance of the latter is emphasized by the normal function of mammalian renal tubules, which reabsorb 99% of the water from glomerular filtrate at the same time that acid is secreted by intercalated cells. Some members of the aquaporin superfamily are permeated by a variety of small neutral solutes such as glycerol or urea (termed “aquaglyceroporins”) (2). The transport of water or glycerol through aquaporins represents facilitated diffusion driven by osmotic or concentration gradients.