Autopromotion of K-Ras4B Feedback Activation Through an SOS-Mediated Long-Range Allosteric Effect.

ABSTRACT: The Ras-specific guanine nucleotide exchange factors Son of Sevenless (SOS) regulates Ras activation by converting inactive GDP-bound to active GTP-bound states. The catalytic activity of Ras is further allosterically regulated by GTP-Ras bound to a distal site through a positive feedback loop. To address the mechanism underlying the long-range allosteric activation of the catalytic K-Ras4B by an additional allosteric GTP-Ras through SOS, we employed molecular dynamics simulation of the K-Ras4B^G13D•SOS^cat complex with and without an allosteric GTP-bound K-Ras4B^G13D. We found that the binding of an allosteric GTP-K-Ras4B^G13D enhanced the affinity between the catalytic K-Ras4B^G13D and SOS^cat, forming a more stable conformation

SUBMITTER: He X 

PROVIDER: S-EPMC9023742 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature