Practice question

Although dynein can bind microtubules and hydrolyze ATP alone in vitro motility assays in vivo most physiological functions require dynactin 1 MDa multiprotein complex discovered as activator of vesicle transport from squid axoplasm. Structure comprises Arp1 actin related protein filament 8 copies forming short filament 37 nm rod barbed end capped by CapZ pointed end by Arp11 p62 p25 p27 complex shoulder arm containing p150Glued DCTN1 with N terminal CAP Gly plus basic microtubule binding domains and long coiled coil dimer interacting with dynein intermediate chain via CC1 box. Dynactin performs dual roles: binding diverse cargo adaptors BicD2 Hook3 Spindly Ninein that select vesicles nuclei kinetochores via coiled coil cargo binding domains and tethering dynein to microtubules via p150Glued MTBD increasing processivity from limited hundred nanometer runs to several microns run length up to 10 microns. Cargo binding relieves dynein autoinhibition converting weak diffusive complex into high force super complex containing two dynein dimers for faster movement. Therefore dynactin links dynein to cargo and enhances processivity not inhibiting.