Interaction of KRas4b with anionic membranes: A special role for PIP₂.

ABSTRACT: KRas4b is a small G-protein whose constitutively active oncogenic mutants are present in 90% of pancreatic cancers. Using fully post-translationally modified KRAS4b, we investigated the role of lipid identity in the recruitment of KRas4b to a membrane surface of defined composition. Application of a newly developed single frequency fluorescence anisotropy decay experiment to this system revealed that KRas4b has a significant binding preference for Nanodisc bilayers containing PIP₂. We conducted molecular dynamics simulations to look for an origin of this specificity. In the case of membranes containing PIP₂ the protein formed long-lived salt bridges with PIP₂ head groups but not the monovalent DMPS, explaining the experimentally observed lipid specificity.

SUBMITTER: Gregory MC 

PROVIDER: S-EPMC5509366 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature