PDF(Pubmed)
Abstract：
Members of the widely conserved progestin and adipoQ receptor (PAQR) family function to maintain membrane homeostasis: membrane fluidity and fatty acid composition in eukaryotes and membrane energetics and fatty acid composition in bacteria. All PAQRs consist of a core seven transmembrane domain structure and five conserved amino acids (three histidines, one serine, and one aspartic acid) predicted to form a hydrolase-like catalytic site. PAQR homologs in Bacteria (called TrhA, for transmembrane homeostasis protein A) maintain homeostasis of membrane charge gradients, like the membrane potential and proton gradient that comprise the proton motive force, but their molecular mechanisms are not yet understood. Here, we show that TrhA in Escherichia coli has a periplasmic C-terminus, which places the five conserved residues shared by all PAQRs at the cytoplasmic interface of the membrane. Here, we characterize several conserved residues predicted to form an active site by site-directed mutagenesis. We also identify a specific role for TrhA in modulating unsaturated fatty acid biosynthesis with conserved residues required to either promote or reduce the abundance of unsaturated fatty acids. We also identify distinct roles for the conserved residues in supporting TrhA\'s role in maintaining membrane energetics homeostasis that suggest that both functions are intertwined and probably partly dependent on one another. An analysis of domain architecture of TrhA-like domains in Bacteria further supports a function of TrhA linking membrane energetics homeostasis with biosynthesis of unsaturated fatty acid in the membrane. IMPORTANCE Progestin and adipoQ receptor (PAQR) family proteins are evolutionary conserved regulators of membrane homeostasis and have been best characterized in eukaryotes. Bacterial PAQR homologs, named TrhA (transmembrane homeostasis protein A), regulate membrane energetics homeostasis through an unknown mechanism. Here, we present evidence linking TrhA to both membrane energetics homeostasis and unsaturated fatty acid biosynthesis. Analysis of domain architecture together with experimental evidence suggests a model where TrhA activity on unsaturated fatty acid biosynthesis is regulated by changes in membrane energetics to dynamically adjust membrane homeostasis.
摘要：
目的：孕激素和脂肪Q受体（PAQR）家族蛋白是进化保守的膜稳态调节因子，在真核生物中得到了最好的表征。细菌PAQR同源物，命名为TrhA（跨膜稳态蛋白A），通过未知的机制调节膜能体内平衡。这里,我们提供了将TrhA与膜能体内平衡和不饱和脂肪酸生物合成联系起来的证据。域结构的分析以及实验证据表明，一种模型，其中TrhA对不饱和脂肪酸生物合成的活性受到膜能学变化的调节，以动态调节膜稳态。
