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Protein & Peptide Letters

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Mini-Review Article

TMEM16A Protein: Calcium-Binding Site and its Activation Mechanism

Author(s): Wanying Ji, Donghong Shi, Sai Shi, Xiao Yang, Yafei Chen, Hailong An and Chunli Pang*

Volume 28, Issue 12, 2021

Published on: 03 December, 2021

Page: [1338 - 1348] Pages: 11

DOI: 10.2174/0929866528666211105112131

Price: $65

Abstract

Abstract: TMEM16A mediates the calcium-activated transmembrane flow of chloride ions and a variety of physiological functions. The binding of cytoplasmic calcium ions of TMEM16A and the consequent conformational changes of it are the key issues to explore the structure-function relationship. In recent years, researchers have explored this issue through electrophysiological experiments, structure resolving, molecular dynamic simulation, and other methods. The structures of TMEM16 family members determined by cryo-Electron microscopy (cryo-EM) and X-ray crystallization provide the primary basis for the investigation of the molecular mechanism of TMEM16A. However, the binding and activation mechanism of calcium ions in TMEM16A are still unclear and controversial. This mini-review discusses four Ca2+ sensing sites of TMEM16A and analyzes activation properties of TMEM16A by them, which will help understand the structure-function relationship of TMEM16A and throw light on the molecular design targeting the TMEM16A channel.

Keywords: TMEM16A, CaCCs, Ca2+-binding site, stereostructure, structure-function relationship, activation mechanism.

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Graphical Abstract

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