Department of Biochemistry and Molecular Biology, Center for Membrane Biology, the University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA.
Theoretical Molecular Biophysics Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Commun Biol. 2023 May 29;6(1):573. doi: 10.1038/s42003-023-04944-6.
Ca is an important signaling messenger. In microorganisms, fungi, and plants, H/Ca antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca in two distinct modes: a low-flux H/Ca exchange mode and a high-flux mode in which Ca and phosphate ions are co-transported (1:1) in exchange for H. Coupling with phosphate greatly accelerates the Ca efflux activity of YfkE. Our studies reveal that Ca and phosphate bind to adjacent sites in a central translocation pathway and lead to mechanistic insights that explain how this CAX alters its conserved alpha-repeat motifs to adopt phosphate as a specific "transport chaperon" for Ca translocation. This finding uncovers a co-transport mechanism within the CAX family that indicates this class of proteins contributes to the cellular homeostasis of both Ca and phosphate.
钙是一种重要的信号信使。在微生物、真菌和植物中，已知 H/Ca 反向转运蛋白（CAX）通过催化其跨细胞膜流出，在细胞内钙的动态平衡中发挥关键作用。在这里，我们揭示了细菌 CAX 同源物 YfkE 以两种不同的模式运输 Ca：低通量的 H/Ca 交换模式和高通量模式，其中 Ca 和磷酸盐离子以 1:1 的比例共同转运（以 H 为交换）。与磷酸盐的偶联极大地加速了 YfkE 的 Ca 外排活性。我们的研究揭示了 Ca 和磷酸盐结合在中央转运途径中的相邻位点上，并导致了机制上的见解，解释了这种 CAX 如何改变其保守的α-重复基序，以采用磷酸盐作为 Ca 转运的特定“运输伴侣”。这一发现揭示了 CAX 家族内的共转运机制，表明这类蛋白质有助于细胞内钙和磷酸盐的动态平衡。
