In a combined chemical-biological and biophysical approach we explored the free energy contributions to the membrane partitioning of Ras proteins, such as N-Ras and K-Ras4B, and compared the theoretical predictions with experimental data on the membrane insertion of Ras proteins of various anchor systems into rationally designed model and natural membrane systems. Various factors fostering or reducing the membrane partitioning properties are discussed, including hydrophobic effects, lipid chain mismatch, electrostatic interactions, membrane-mediated protein-protein interactions, and terms that account for line tension effects between coexisting lipid domains or lipid sorting and change the lateral organization of the lipid bilayer system. For heterogeneous membranes, localization and sequestration at domain boundaries as well as formation of protein clusters and collective lateral organization via an effective lipid sorting mechanism provide complementary ways of inducing membrane nanodomains that could potentially operate as effective signaling platforms. Finally, we show data on the effect of co-localization of different Ras proteins and their interaction partners on the lateral membrane organization.<br/>

Membrane-associated signaling proteins: The role of the lipid anchor in membrane partitioning processes

2019 Spring National Meeting

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