The small GTPase MRAS is a broken switch.

ABSTRACT: Intense research on founding members of the RAS superfamily has defined our understanding of these critical signalling proteins, leading to the premise that small GTPases function as molecular switches dependent on differential nucleotide loading. The closest homologs of H/K/NRAS are the three-member RRAS family, and interest in the MRAS GTPase as a regulator of MAPK activity has recently intensified. We show here that MRAS does not function as a classical switch and is unable to exchange GDP-to-GTP in solution or when tethered to a lipid bilayer. The exchange defect is unaffected by inclusion of the GEF SOS1 and is conserved in a distal ortholog from nematodes. Synthetic activating mutations widely used to study the function of MRAS in a presumed GTP-loaded state do not increase exchange,

SUBMITTER: Bernal Astrain G 

PROVIDER: S-EPMC11733253 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature