甘油对大肠杆菌水甘油孔蛋白GlpF透水的调节作用
Glycerol Modulates Water Permeation through Escherichia coli Aquaglyceroporin GlpF
摘要：
在跨细胞膜运输水和甘油的水甘油孔蛋白中，大肠杆菌甘油摄取促进剂（GlpF）是研究最彻底的。然而，一个问题仍然存在：甘油调节水渗透？这项研究回答了这个基本问题，通过确定甘油的化学电位分布沿渗透路径通过GlpF的导电孔。Asn-Pro-Ala（NPA）基序附近有一个深井（解离常数14 μ M），选择性过滤器附近有一个屏障（高于井底10.1 kcal/mol）。这种配置文件的存在归功于GlpF的完美空间排列：甘油-蛋白质范德华相互作用在NPA附近是有吸引力的，但在导电孔的其他地方是排斥的。鉴于水和甘油在GlpF的两亲性孔中排成单行的性质，得出以下结论：甘油在微米范围内调节水的渗透。在mM浓度下，GlpF是甘油饱和的，并且停留在孔中的甘油堵塞了传导孔。因此，水渗透与甘油解离完全相关，其具有6.5 kcal/mol的Arrhenius活化势垒。这一理论的验证是基于现有的体外数据，其中一些数据没有得到应有的重视：发现水渗透的Arrhenius活化屏障为7 kcal/mol，甘油渗透的Arrhenius活化屏障为9.6 kcal/mol;高达100 mM甘油的存在不影响渗透性非常低的水运输动力学，这与预测高渗透性（0 M甘油）的现有理论明显矛盾。
英文摘要：
Among aquaglyceroporins that transport both water and glycerol across the cell membrane, Escherichia coli glycerol uptake facilitator (GlpF) is the most thoroughly studied. However, one question remains: Does glycerol modulate water permeation? This study answers this fundamental question by determining the chemical-potential profile of glycerol along the permeation path through GlpF's conducting pore. There is a deep well near the Asn-Pro-Ala (NPA) motifs (dissociation constant 14 microM) and a barrier near the selectivity filter (10.1 kcal/mol above the well bottom). This profile owes its existence to GlpF's perfect steric arrangement: The glycerol-protein van der Waals interactions are attractive near the NPA but repulsive elsewhere in the conducting pore. In light of the single-file nature of waters and glycerols lining up in GlpF's amphipathic pore, it leads to the following conclusion: Glycerol modulates water permeation in the microM range. At mM concentrations, GlpF is glycerol-saturated and a glycerol dwelling in the well occludes the conducting pore. Therefore, water permeation is fully correlated to glycerol dissociation that has an Arrhenius activation barrier of 6.5 kcal/mol. Validation of this theory is based on the existent in vitro data, some of which have not been given the proper attention they deserved: The Arrhenius activation barriers were found to be 7 kcal/mol for water permeation and 9.6 kcal/mol for glycerol permeation; The presence of up to 100 mM glycerol did not affect the kinetics of water transport with very low permeability, in apparent contradiction with the existent theories that predicted high permeability (0 M glycerol).
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
