Lipid scrambling is a general feature of protein insertases

• DOI: 10.1073/pnas.2319476121
• Publication Date: 2024-04-15T19:06:53Z
• Authors: Dazhi Li; Cristian Rocha-Roa; Matthew A. Schilling; Karin M. Reinisch; Stefano Vanni
• Keywords: Membrane contact site; Peripheral membrane protein; Scrambling; Phospholipid scramblase; Glycerophospholipids; Organelle; Membrane Lipids

Glycerophospholipids are synthesized primarily in the cytosolic leaflet of endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow ER membranes derived from it grow. Lipid equilibration is facilitated by integral proteins called “scramblases.” These feature a hydrophilic groove allowing polar heads lipids traverse hydrophobic interior, similar credit card moving through reader. Nevertheless, despite their fundamental role expansion dynamics, identity most scramblases has remained elusive. Here, combining biochemical reconstitution molecular dynamics simulations, we show that lipid scrambling general protein insertases, which insert polypeptide chains into organelles disconnected vesicle trafficking. Our data indicate occurs same channel insertion takes place abolished presence nascent chains. We propose insertases could have so-far-overlooked as scramblases.