Speaker: Paola Llinas, MIKICA team, I2BC
Title: Molecular characterization of the interaction of JIP3 and JIP4 adaptors with the kinesin heavy chain, KIF5B : insights on the complexity of coiled coil interactions in kinesin-1 regulation
Abstract:
Intracellular transport is highly regulated; one key mechanism is the autoinhibition of molecular motors and adaptor proteins. Although progress has been made in understanding how kinesin autoinhibition works, crucial details about its activation—particularly how cargo-motor adaptors regulate it—are still unknown. JIP3 and JIP4 are adaptors that activate kinesin-1 and dynein-dynactin motors, enabling bidirectional transport along microtubules. I will talk about the characterization of the interaction between the kinesin-1 heavy chain, KIF5B, and both JIP3 and JIP4 (JIP3/4), using extensive site-directed mutagenesis and binding experiments associated with modelling. We determined the regions of JIP3/4 and KIF5B required for interaction, identify differences between JIP3 and JIP4 that can modulate this interaction and propose a mechanism in which an extended charged surface with multiple weak-affinity sites would be needed to bind the kinesin-1 heavy chain for activation. It will be the occasion to talk about the complexity of coiled coil interactions in kinesin-1 regulation that are challenging for Alpha Fold prediction.