甲酸转运蛋白FocA的分子结构揭示其是以五聚体形式存在的一个通道蛋白

FocA是甲酸-亚硝酸转运蛋白家族(FNT)的一个代表性成员,在细菌、古细菌、真菌、藻类和寄生虫中负责短链酸的转运。甲酸-亚硝酸转运蛋白家族中所有成员蛋白的分子结构和转运机制都是未知的。在这项工作中,我们解析了大肠杆菌中FocA蛋白的三维晶体结构,分辨率高达2.25。这个晶体结构显示,FocA构成了一个对称的五聚体,其中每个单体包含6个跨膜螺旋片段。而且,尽管FocA与水通道蛋白Aquaporin在序列上缺乏同源性,但它们的单体整体结构却异常相似。这些结果意味着FocA应该是一个跨膜通道蛋白,而不是此前认为的转运蛋白。进一步的结构分析识别出了通道中的重要氨基酸残基,明确了通道路径,并揭示了两个对通道起收紧作用的位点。但是与水通道蛋白Aqua-porin不同,FocA对水分子并没有通透性,却允许甲酸通过。在结构生物学和生物化学方面的进一步研究为阐明FocA的通道活性机理提供了重要线索。

Structure of The Formate Transporter Foca Reveals A Pentameric Aquaporin-Like Channel

FocA is a representative member of the formate-nitrite transporter family,which transports short-chain acids in bacteria,archaea,fungi,algae and parasites.The structure and transport mechanism of the formate-nitrite transporter family remain unknown.Here we report the crystal structure of Escherichia coli FocA at 2.25 resolution.FocA forms a symmetric pentamer,with each protomer consisting of six transmembrane segments.Despite a lack of sequence homology,the overall structure of the FocA protomer closely resembles that of aquaporin and strongly argues that FocA is a channel,rather than a transporter.Structural analysis identifies potentially important channel residues,defines the channel path and reveals two constriction sites.Unlike aquaporin,FocA is impermeable to water but allows the passage of formate.A structural and biochemical investigation provides mechanistic insights into the channel activity of FocA.