Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior.

ABSTRACT: The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the pr

SUBMITTER: Goswami D 

PROVIDER: S-EPMC7060043 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature