Calmodulin extracts the Ras family protein RalA from lipid bilayers by engagement with two membrane-targeting motifs.

ABSTRACT: RalA is a small GTPase and a member of the Ras family. This molecular switch is activated downstream of Ras and is widely implicated in tumor formation and growth. Previous work has shown that the ubiquitous Ca²⁺-sensor calmodulin (CaM) binds to small GTPases such as RalA and K-Ras4B, but a lack of structural information has obscured the functional consequences of these interactions. Here, we have investigated the binding of CaM to RalA and found that CaM interacts exclusively with the C terminus of RalA, which is lipidated with a prenyl group in vivo to aid membrane attachment. Biophysical and structural analyses show that the two RalA membrane-targeting motifs (the prenyl anchor and the polybasic motif) are engaged by distinct lobes of CaM and that CaM binding leads to removal

SUBMITTER: Chamberlain SG 

PROVIDER: S-EPMC8433508 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature