Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases

Membrane sorting of Ras and its isolated lipid anchor is based on membrane curvature, sensed by Ras itself. This helps to explain the previous inability to match in vivo results in vitro in promoting the raftophilic Ras to partition with membrane lipid rafts. Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general.