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Molecular insights into lipid-assisted Ca2+ regulation of the TRP channel Polycystin-2

Wilkes, Martin ; Madej, M Gregor ; Kreuter, Lydia ; Rhinow, Daniel ; Heinz, Veronika ; De Sanctis, Silvia ; Ruppel, Sabine ; Richter, Rebecca M ; Joos, Friederike ; Grieben, Marina ; Pike, Ashley C W ; Huiskonen, Juha T ; Carpenter, Elisabeth P ; Kühlbrandt, Werner ; Witzgall, Ralph ; Ziegler, Christine



Abstract

Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca2+ signaling pathways. Malfunctioning Ca2+ regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter ...

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