Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex

Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope(1). Here, we discovered an unexpected role for yeast dynein light chain (Dyn2) 2 in the NPC. Dyn2 is a previously undescribed nucleoporin that functions as molecular glue to dimerize and stabilize the Nup82-Nsp1-Nup159 complex, a module of the cytoplasmic pore filaments(3). Biochemical analyses showed that Dyn2 binds to a linear motif ( termed DIDNup159) inserted between the Phe-Gly repeat and coiled-coil domain of Nup159. Electron microscopy revealed that the reconstituted Dyn2 DIDNup159 complex forms a rigid rod-like structure, in which five Dyn2 homodimers align like 'pearls on a string' between two extented DIDNup159 strands. These findings imply that the rigid 20 nm long Dyn2-DIDNup159 filament projects the Nup159 Phe-Gly repeats from the Nup82 module. Thus, it is possible that dynein light chain plays a role in organizing natively unfolded Phe-Gly repeats within the NPC scaffold to facilitate nucleocytoplasmic transport.