The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase

Abstract

Dissecting membrane dislocation Mistargeting and misinsertion of membrane proteins causes proteostasis stress and dysfunction of intracellular organelles, which can lead to disease. McKenna et al. found that a conserved orphan P-type adenosine triphosphatase (ATPase) transporter removes misinserted transmembrane segments from the endoplasmic reticulum (ER). Functional reconstitutions and cryo–electron microscopy structures show how this ATPase selectively extracts mitochondrial proteins that are mistargeted to the ER and transmembrane segments that are inserted in the wrong orientation. This work identifies polypeptides as a new class of P-type ATPase substrates and defines a new protein quality-control mechanism at the ER. Science , this issue p. eabc5809