Gating mechanism of the extracellular entry to the lipid pathway in a TMEM16 scramblase.

ABSTRACT: Members of the TMEM16/ANO family of membrane proteins are Ca²⁺-activated phospholipid scramblases and/or Cl^- channels. A membrane-exposed hydrophilic groove in these proteins serves as a shared translocation pathway for ions and lipids. However, the mechanism by which lipids gain access to and permeate through the groove remains poorly understood. Here, we combine quantitative scrambling assays and molecular dynamic simulations to identify the key steps regulating lipid movement through the groove. Lipid scrambling is limited by two constrictions defined by evolutionarily conserved charged and polar residues, one extracellular and the other near the membrane mid-point. The region between these constrictions is inaccessible to lipids and water molecules, suggesting tha

SUBMITTER: Lee BC 

PROVIDER: S-EPMC6092359 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature