Lipid scrambling is a general feature of protein insertases

• 成果类型: Article
• 署名作者: Li, Dazhi; Rocha-Roa, Cristian; Schilling, Matthew A.; Reinisch, Karin M.; Vanni, Stefano
• 署名单位: Yale University; University of Fribourg; University of Fribourg
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10692
• DOI: 10.1073/pnas.2319476121
• 发表日期: 2024-04-23
• 关键词: structural basis; membrane; mitochondria; biogenesis; insertion; FAMILY; yidc

摘要

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