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Publication Abstract from PubMed

Chloride channels (CLCs) transport anion across membrane to regulate ion homeostasis and acidification of intracellular organelles, and are divided into anion channels and anion/proton antiporters. Arabidopsis thaliana CLCa (AtCLCa) transporter localizes to the tonoplast which imports NO(3)(-) and to a less extent Cl(-) from cytoplasm. The activity of AtCLCa and many other CLCs is regulated by nucleotides and phospholipids, however, the molecular mechanism remains unclear. Here we determine the cryo-EM structures of AtCLCa bound with NO(3)(-) and Cl(-), respectively. Both structures are captured in ATP and PI(4,5)P(2) bound conformation. Structural and electrophysiological analyses reveal a previously unidentified N-terminal beta-hairpin that is stabilized by ATP binding to block the anion transport pathway, thereby inhibiting the AtCLCa activity. While AMP loses the inhibition capacity due to lack of the beta/gamma- phosphates required for beta-hairpin stabilization. This well explains how AtCLCa senses the ATP/AMP status to regulate the physiological nitrogen-carbon balance. Our data further show that PI(4,5)P(2) or PI(3,5)P(2) binds to the AtCLCa dimer interface and occupies the proton-exit pathway, which may help to understand the inhibition of AtCLCa by phospholipids to facilitate guard cell vacuole acidification and stomatal closure. In a word, our work suggests the regulatory mechanism of AtCLCa by nucleotides and phospholipids under certain physiological scenarios and provides new insights for future study of CLCs.

Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids.,Yang Z, Zhang X, Ye S, Zheng J, Huang X, Yu F, Chen Z, Cai S, Zhang P Nat Commun. 2023 Aug 12;14(1):4879. doi: 10.1038/s41467-023-40624-z. PMID:37573431^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.