title: Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex.
abstract: Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. Here, we discovered an unexpected role for yeast dynein light chain (Dyn2) 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. Biochemical analyses showed that Dyn2 binds to a linear motif (termed DID(Nup159)) inserted between the Phe-Gly repeat and coiled-coil domain of Nup159. Electron microscopy revealed that the reconstituted Dyn2-DID(Nup159) complex forms a rigid rod-like structure, in which five Dyn2 homodimers align like 'pearls on a string' between two extented DID(Nup159) strands. These findings imply that the rigid 20 nm long Dyn2-DID(Nup159) 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.
authors.affiliation: Biochemie-Zentrum der Universität Heidelberg (BZH), Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stelter
authors.forename: Ruth
authors.initials: R
authors.lastname: Kunze
authors.forename: Dirk
authors.initials: D
authors.lastname: Flemming
authors.forename: Dominic
authors.initials: D
authors.lastname: Höpfner
authors.forename: Meikel
authors.initials: M
authors.lastname: Diepholz
authors.forename: Peter
authors.initials: P
authors.lastname: Philippsen
authors.forename: Bettina
authors.initials: B
authors.lastname: Böttcher
authors.forename: Ed
authors.initials: E
authors.lastname: Hurt
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D019281:Dimerization; D004398:Dyneins / Q000502:physiology*; D006801:Humans; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000502:physiology*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
chemical_list: C093510:NUP159 protein, S cerevisiae; C095897:NUP82 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; D004398:Dyneins