Deciphering lipid codes: K ‐Ras as a paradigm

The cell plasma membrane (PM) is a highly dynamic and heterogeneous lipid environment, driven by complex hydrophobic and electrostatic interactions among the hundreds of types of lipid species. Although the biophysical processes governing lipid lateral segregation in the cell PM have been established in vitro, biological implications of lipid heterogeneity are poorly understood. Of particular interest is how membrane proteins potentially utilize transient spatial clustering of PM lipids to regulate function. The current review focuses on a lipid anchored small GTPase K‐Ras as an example to explore how its C‐terminal membrane‐anchoring domain, consisting of a contiguous hexa‐lysine polybasic domain and an adjacent farnesyl anchor, possesses a complex coding mechanism for highly selective lipid sorting on the PM. How this lipid specificity modulates K‐Ras signal transmission will also be discussed. Synopsis Plasma membrane is a highly heterogeneous environment and contains various nano‐domains with distinct local lipid composition. Lipid‐anchored small GTPases Ras proteins use their C‐terminal membrane anchoring features for specific lipid sorting. In particular, K‐Ras has a C‐terminal hexa‐lysine polybasic domain and an adjacent farnesyl anchor, which together allow the capability to selectively sort acidic phosphatidylserine lipids in the inner leaflet of the plasma membrane. The current review summarizes the latest findings in K‐Ras selective lipid s...
Source: Traffic - Category: Research Authors: Tags: REVIEW Source Type: research