Your browser doesn't support javascript.
loading
TMEM16 and TMEM63/OSCA proteins share a conserved potential to permeate ions and phospholipids.
Lowry, Augustus J; Liang, Pengfei; Wan, Y C Serena; Pei, Zhen-Ming; Yang, Huanghe; Zhang, Yang.
Afiliación
  • Lowry AJ; Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
  • Liang P; Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
  • Wan YCS; Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
  • Pei ZM; Department of Biology, Duke University, Durham, NC 27710, USA.
  • Yang H; Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
  • Zhang Y; Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
bioRxiv ; 2024 Feb 05.
Article en En | MEDLINE | ID: mdl-38370744
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, likely function solely as ion channels. However, the remaining 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 lysine mutations in transmembrane helix (TM) 4 allow non-scrambling TCS members to permeate phospholipids. 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.

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article