Recent progress in structural studies on TMEM16A channel

Sai Shi; Chunli Pang; Shuai Guo; Yafei Chen; Biao Ma; Chang Qu; Qiushuang Ji; Hailong An

doi:10.1016/j.csbj.2020.03.015

Recent progress in structural studies on TMEM16A channel

Comput Struct Biotechnol J. 2020 Mar 21:18:714-722. doi: 10.1016/j.csbj.2020.03.015. eCollection 2020.

Authors

Sai Shi^{1

2

3}, Chunli Pang³, Shuai Guo^{1

2

3}, Yafei Chen³, Biao Ma^{1

2

3}, Chang Qu^{1

2

3}, Qiushuang Ji³, Hailong An^{1

2

3}

Affiliations

¹ State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300401, China.
² Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province, Hebei University of Technology, Tianjin 300401, China.
³ Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Science, Hebei University of Technology, Tianjin, 300401, China.

Abstract

The calcium-activated chloride channel, also known as TMEM16A, shows both calcium and membrane potential dependent activation. The channel is expressed broadly and contributes to a variety of physiological processes, and it is expected to be a target for the treatment of diseases such as hypertension, pain, cystic fibrosis and lung cancer. A thorough understanding of the structural characteristics of TMEM16A is important to reveal its physiological and pathological roles. Recent studies have released several Cryo-EM structures of the channel, revealed the structural basis and mechanism of the gating of the channel. This review focused on the understandings of the structural basis and molecular mechanism of the gating and permeation of TMEM16A channel, which will provide important basis for the development of drugs targeting TMEM16A.

Keywords: CaCCs; Drug target; Ion channel; Molecular mechanism; Structure; TMEM16A.

Publication types

Review