Lipid Scrambling Pathways in the Sec61 Translocon Complex.

ABSTRACT: Cellular homeostasis depends on the rapid, ATP-independent translocation of newly synthesized lipids across the endoplasmic reticulum (ER) membrane. Lipid translocation is facilitated by membrane proteins known as scramblases, a few of which have recently been identified in the ER. Our previous structure of the translocon-associated protein (TRAP) bound to the Sec61 translocation channel revealed local membrane thinning, suggesting that the Sec61/TRAP complex might be involved in lipid scrambling. Using complementary fluorescence spectroscopy assays, we detected nonselective scrambling by reconstituted translocon complexes. This activity was unaffected by Sec61 inhibitors that block its lateral gate, suggesting a second lipid scrambling pathway within the complex. Molecular dynamics simula

SUBMITTER: Javanainen M 

PROVIDER: S-EPMC12082634 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature