Activation Stoichiometry and Pore Architecture of TRPA1 Probed with Channel Concatemers.

ABSTRACT: The nociceptor ion channel TRPA1 detects a wide range of hazardous chemicals, including reactive electrophiles such as cinnamaldehyde, which gate the channel allowing Na⁺ and Ca²⁺ entry. TRPA1 assembles as a tetramer, with a central pore within which an aspartate residue (D918) determines Ca²⁺ permeability. Here, we report that introduction of histidine at this position, D918H, makes TRPA1 channels sensitive to block by nanomolar concentration of Zn²⁺ and can be used to functionally tag subunits in concatemers. Concatemers with increasing numbers of D918H subunits display increasing sensitivity to Zn²⁺ inhibition, indicating that the four side chains at position 918 of the tetramer directly coordinate Zn²⁺ and other permeati

SUBMITTER: Ye W 

PROVIDER: S-EPMC6244152 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature