Structural basis for activation of voltage sensor domains in an ion channel TPC1.

ABSTRACT: Voltage-sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino acids inside each sensor cooperatively respond to changes in voltage. Our previous structure of a TPC1 channel captured an example of a resting-state VSD in an intact ion channel. To generate an activated-state VSD in the same channel we removed the luminal inhibitory Ca²⁺-binding site (Ca_i²⁺), which shifts voltage-dependent opening to more negative voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the VSD, an intermediate state 1 that partially closes access to the cytoplasmic side but remains occluded on the luminal side and an intermediate

SUBMITTER: Kintzer AF 

PROVIDER: S-EPMC6166827 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature