The Structural Basis of the Farnesylated and Methylated KRas4B Interaction with Calmodulin.

ABSTRACT: Ca²⁺-calmodulin (CaM) extracts KRas4B from the plasma membrane, suggesting that KRas4B/CaM interaction plays a role in regulating Ras signaling. To gain mechanistic insight, we provide a computational model, supported by experimental structural data, of farnesylated/methylated KRas4B_1-185 interacting with CaM in solution and at anionic membranes including signaling lipids. Due to multiple interaction modes, we observe diverse conformational ensembles of the KRas4B-CaM complex. A highly populated conformation reveals the catalytic domain interacting with the N-lobe and the hypervariable region (HVR) wrapping around the linker with the farnesyl docking to the extended CaM's C-lobe pocket. Alternatively, KRas4B can interact with collapsed CaM with the farnesyl penetratin

SUBMITTER: Jang H 

PROVIDER: S-EPMC8194365 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature