Phosphoinositide regulates dynamic movement of the S4 voltage sensor in the second repeat in two-pore channel 3.

ABSTRACT: The two-pore channels (TPCs) are voltage-gated cation channels consisting of single polypeptides with two repeats of a canonical 6-transmembrane unit. TPCs are known to be regulated by various physiological signals such as membrane voltage and phosphoinositide (PI). The fourth helix in the second repeat (second S4) plays a major role in detecting membrane voltage, whereas the first repeat contains a PI binding site. Therefore, each of these stimuli is detected by a unique repeat to regulate the gating of the TPC central pore. How these various stimuli regulate the dynamic structural rearrangement of the TPC molecule remain unknown. Here, we found that PI binding to the first repeat in TPC3 regulates the movement of the distally located second S4 helix, showing that the PI-binding signal is

SUBMITTER: Hirazawa K 

PROVIDER: S-EPMC8665364 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature