The formate channel FocA exports the products of mixed-acid fermentation
The formate channel FocA exports the products of mixed-acid fermentation
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DOI：
10.1073/pnas.1204201109
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发表时间：
2012-08-14
影响因子：
11.1
通讯作者：
Andrade, Susana L. A.
中科院分区：
文献类型：
--
作者：
Lue, Wei;Du, Juan;Andrade, Susana L. A.
甲酸盐是许多肠细菌在葡萄糖厌氧发酵中的主要代谢产物。通过五聚体离子通道/转运蛋白福卡（FocA）跨细胞膜转运，该转运蛋白与亚硝酸盐通道NirC一起形成甲酸盐/亚硝酸盐转运蛋白（FNT）家族。在这里，我们已经进行了电生理分析的福卡从鼠伤寒沙门氏菌的通道特性和评估其对甲酸和其他可能的渗透离子的特异性。甲酸盐，次磷酸盐和亚硝酸盐的单通道电流揭示了两种机制不同的门控模式，反映了每个福卡原体的运输通道中不同类型的结构重排。此外，福卡不进行阳离子或二价阴离子，但氯阴离子被确定为进一步运输的物种，沿着与乙酸，乳酸和丙酮酸。甲酸盐、乙酸盐和乳酸盐是厌氧混合酸发酵的主要终产物，该途径主要需要福卡，因此该通道理想地适于充当多功能输出蛋白以防止其细胞内积累。由于在FNT家族成员中形成转运通道的残基的高度保守性，传导多个分子的灵活性最有可能是这些蛋白质的一般特征。
Formate is a major metabolite in the anaerobic fermentation of glucose by many enterobacteria. It is translocated across cellular membranes by the pentameric ion channel/transporter FocA that, together with the nitrite channel NirC, forms the formate/nitrite transporter (FNT) family of membrane transport proteins. Here we have carried out an electrophysiological analysis of FocA from Salmonella typhimurium to characterize the channel properties and assess its specificity toward formate and other possible permeating ions. Single-channel currents for formate, hypophosphite and nitrite revealed two mechanistically distinct modes of gating that reflect different types of structural rearrangements in the transport channel of each FocA protomer. Moreover, FocA did not conduct cations or divalent anions, but the chloride anion was identified as further transported species, along with acetate, lactate and pyruvate. Formate, acetate and lactate are major end products of anaerobic mixed-acid fermentation, the pathway where FocA is predominantly required, so that this channel is ideally adapted to act as a multifunctional export protein to prevent their intracellular accumulation. Because of the high degree of conservation in the residues forming the transport channel among FNT family members, the flexibility in conducting multiple molecules is most likely a general feature of these proteins.