Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane.

ABSTRACT: The small GTPase KRAS is localized at the plasma membrane where it functions as a molecular switch, coupling extracellular growth factor stimulation to intracellular signaling networks. In this process, KRAS recruits effectors, such as RAF kinase, to the plasma membrane where they are activated by a series of complex molecular steps. Defining the membrane-bound state of KRAS is fundamental to understanding the activation of RAF kinase and in evaluating novel therapeutic opportunities for the inhibition of oncogenic KRAS-mediated signaling. We combined multiple biophysical measurements and computational methodologies to generate a consensus model for authentically processed, membrane-anchored KRAS. In contrast to the two membrane-proximal conformations previously reported, we identify a thi

SUBMITTER: Van QN 

PROVIDER: S-EPMC7533834 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature