Computational Modeling Reveals that Signaling Lipids Modulate the Orientation of K-Ras4A at the Membrane Reflecting Protein Topology.

ABSTRACT: The structural, dynamical, and functional characterization of the small GTPase K-Ras has become a research area of intense focus due to its high occurrence in human cancers. Ras proteins are only fully functional when they interact with the plasma membrane. Here we present all-atom molecular dynamics simulations (totaling 5.8 μs) to investigate the K-Ras4A protein at membranes that contain anionic lipids (phosphatidyl serine or phosphatidylinositol bisphosphate). We find that similarly to the homologous and highly studied K-Ras4B, K-Ras4A prefers a few distinct orientations at the membrane. Remarkably, the protein surface charge and certain lipids can strongly modulate the orientation preference. In a novel analysis, we reveal that the electrostatic interaction (attraction but also repulsi

SUBMITTER: Li ZL 

PROVIDER: S-EPMC6178820 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature