Kendra Marcus

Abstract Clamp loaders are AAA+ ATPases that facilitate high-speed DNA replication. In eukaryotic and bacteriophage clamp loaders, ATP hydrolysis requires interactions between aspartate residues in one protomer, present in conserved ‘DEAD-box’ motifs, and arginine residues in adjacent protomers. We show that functional defects resulting from a DEAD-box mutation in the T4 bacteriophage clamp loader can be compensated by widely distributed single mutations in the ATPase domain.

Highlights • CaM exhibits multiple modes of interaction in complex with FME KRas4B1-185-GTP • KRas4B-CaM yields a highly populated L-shaped molecular topology with extended CaM • CaM mainly targets the polybasic HVR, sequestering the farnesyl group • The signaling lipids can prevent the departure of KRas4B from the membrane Summary Ca2+-calmodulin (CaM) extracts KRas4B from the plasma membrane, suggesting that KRas4B/CaM interaction plays a role in regulating Ras signaling.