Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output.

ABSTRACT: K-Ras is targeted to the plasma membrane by a C-terminal membrane anchor that comprises a farnesyl-cysteine-methyl-ester and a polybasic domain. We used quantitative spatial imaging and atomistic molecular dynamics simulations to examine molecular details of K-Ras plasma membrane binding. We found that the K-Ras anchor binds selected plasma membrane anionic lipids with defined head groups and lipid side chains. The precise amino acid sequence and prenyl group define a combinatorial code for lipid binding that extends beyond simple electrostatics; within this code lysine and arginine residues are non-equivalent and prenyl chain length modifies nascent polybasic domain lipid preferences. The code is realized by distinct dynamic tertiary structures of the anchor on the plasma membrane that go

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC5653213 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature