Structure and activation mechanism of TMEM206
EMSL Project ID
51266
Abstract
Proton activated channels are ion-permeable channels that are rapidly activated by extracellular acidification. With their activation levels falling well below physiological pH, these channels facilitate signaling in pathological conditions that cause tissue acidification, such as ischemia, tumor growth, and inflammation. Although in the past decade much has been uncovered about the proton-activated Na+ channels, the Acid-sensing ion channels (ASICs), very little is known about anion permeable proton-activated channels. The chloride permeable channel, Acid-Sensing Outwardly Rectifying Channel (ASOR) was recently identified as the previously uncharacterized gene, TMEM206 (transmembrane protein 206), now commonly referred to as the Proton-Activated Chloride Channel (PAC) (Ullrich et al. eLife 2019; Yang et al, Science 2019). TMEM206 has been implicated to form ASOR’s pore directly, but the structure and mechanism of TMEM206 remains elusive, limiting our understanding of its gating mechanism. The objective of this project is to elucidate the structure of TMEM206 in the near-native lipid environment by single particle cryoEM. Which, in turn, will provide fundamental insight into the activation mechanism and general architecture of TMEM206, which will increase our understanding of TMEM206’s role in acid-induced cell death.
Project Details
Start Date
2020-02-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members