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Journal Article Epublish 3 citations

PubMed: 39495104 DOI: 10.7554/eLife.96957

TMEM16 and OSCA/TMEM63 proteins share a conserved potential to permeate ions and phospholipids.

Elife 13

Authors: Augustus J Lowry, Pengfei Liang, Mo Song, Yuichun Wan, Zhen-Ming Pei, Huanghe Yang, Yang Zhang

Affiliations

  • Department of Biochemistry, Duke University School of Medicine, Durham, United States.
  • Institute of Molecular Physiology, Shenzhen Bay Laboratory, Guangdong, China.
  • Department of Biology, Duke University, Durham, United States.
  • Department of Neurobiology, Duke University School of Medicine, Durham, United States.

Abstract

The calcium-activated TMEM16 proteins and the mechanosensitive/osmolarity-activated OSCA/TMEM63 proteins belong to the Transmembrane Channel/Scramblase (TCS) superfamily. Within the superfamily, OSCA/TMEM63 proteins, as well as TMEM16A and TMEM16B, are thought to function solely as ion channels. However, most TMEM16 members, including TMEM16F, maintain an additional function as scramblases, rapidly exchanging phospholipids between leaflets of the membrane. Although recent studies have advanced our understanding of TCS structure-function relationships, the molecular determinants of TCS ion and lipid permeation remain unclear. Here, we show that single mutations along the transmembrane helix (TM) 4/6 interface allow non-scrambling TCS members to permeate phospholipids. In particular, this study highlights the key role of TM 4 in controlling TCS ion and lipid permeation and offers novel insights into the evolution of the TCS superfamily, suggesting that, like TMEM16s, the OSCA/TMEM63 family maintains a conserved potential to permeate ions and phospholipids.

MeSH

Biological Science Disciplines, Ion Channels, Membranes, Phospholipids

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