Molecular assemblies of the catalytic domain of SOS with KRas and oncogenic mutants.

ABSTRACT: Ras is regulated by a specific guanine nucleotide exchange factor Son of Sevenless (SOS), which facilitates the exchange of inactive, GDP-bound Ras with GTP. The catalytic activity of SOS is also allosterically modulated by an active Ras (Ras-GTP). However, it remains poorly understood how oncogenic Ras mutants interact with SOS and modulate its activity. Here, native ion mobility-mass spectrometry is employed to monitor the assembly of the catalytic domain of SOS (SOS^cat) with KRas and three cancer-associated mutants (G12C, G13D, and Q61H), leading to the discovery of different molecular assemblies and distinct conformers of SOS^cat engaging KRas. We also find KRas^G13D exhibits high affinity for SOS^cat and is a potent allosteric modulator of its

SUBMITTER: Moghadamchargari Z 

PROVIDER: S-EPMC8000204 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature