Wang Kun, Ma Chunhui, Chen Guanglin, Yang Zhisen, Gao Yongxiang, Zhang Zhiyong, Liu Xin, Sun Linfeng
Department of Neurology, First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Physics and Anhui Center for Fundamental Sciences in Theoretical Physics, University of Science and Technology of China, Hefei, China.
Nat Plants. 2025 Sep 2. doi: 10.1038/s41477-025-02104-8.
Calcium homeostasis is tightly regulated due to the essential roles of calcium ions (Ca) in various cellular processes. CAX1 in Arabidopsis thaliana (AtCAX1) serves as a Ca/H exchanger transporting excess cytosolic Ca into the vacuole, which is modulated by kinase phosphorylation in response to diverse signals. However, the regulatory mechanism remains unclear. Here we present the structures of wild-type AtCAX1 in an inactivated state and a phosphomimetic mutant in an activated state. In the wild-type structure, the amino-terminal region forms an α-helix that blocks the transport tunnel, thus inhibiting its transport activity. In contrast, in the phosphomimetic mutant structure, this blocking helix is released from the tunnel, leading to AtCAX1 activation. Conformational changes are also observed in the transmembrane domain. Together, these findings provide insights into the transport mechanism of the Ca/H exchangers and set up a basis for future studies of the regulation of calcium homeostasis in plants.
由于钙离子（Ca）在各种细胞过程中发挥着重要作用，钙稳态受到严格调控。拟南芥中的CAX1（AtCAX1）作为一种Ca/H交换蛋白，将过量的胞质Ca转运到液泡中，它会响应多种信号通过激酶磷酸化进行调节。然而，其调控机制仍不清楚。在此，我们展示了处于失活状态的野生型AtCAX1和处于激活状态的拟磷酸化突变体的结构。在野生型结构中，氨基末端区域形成一个α螺旋，该螺旋阻塞了运输通道，从而抑制其运输活性。相比之下，在拟磷酸化突变体结构中，这个阻塞螺旋从通道中释放出来，导致AtCAX1激活。在跨膜结构域也观察到了构象变化。这些发现共同为Ca/H交换蛋白的运输机制提供了见解，并为未来研究植物钙稳态的调控奠定了基础。
