Structural insights into the complex of oncogenic KRas4B^G12V and Rgl2, a RalA/B activator.

ABSTRACT: About a quarter of total human cancers carry mutations in Ras isoforms. Accumulating evidence suggests that small GTPases, RalA, and RalB, and their activators, Ral guanine nucleotide exchange factors (RalGEFs), play an essential role in oncogenic Ras-induced signalling. We studied the interaction between human KRas4B and the Ras association (RA) domain of Rgl2 (Rgl2^RA), one of the RA-containing RalGEFs. We show that the G12V oncogenic KRas4B mutation changes the interaction kinetics with Rgl2^RA The crystal structure of the KRas4B^G12V: Rgl2^RA complex shows a 2:2 heterotetramer where the switch I and switch II regions of each KRas^G12V interact with both Rgl2^RA molecules. This structural arrangement is highly similar to the HR

SUBMITTER: Tariq M 

PROVIDER: S-EPMC10576006 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature