Gaik et al. describe the P-shaped structure of a key protein complex at the cytoplasmic face of nuclear pores.
The nuclear pore complex (NPC) consists of ∼30 different nucleoporins, most of which are organized into stable subcomplexes. The Nup82 subcomplex, comprising the nucleoporins Nup82, Nup159, Nsp1, and the dynein light chain Dyn2, localizes to the cytoplasmic face of NPCs where it promotes mRNA export. How the subcomplex assembles and fits in to the rest of the NPC is unclear, however.
Gaik et al. purified the Nup82 complex from yeast and analyzed its structure using several different techniques. Most Nup82 complexes contained 2 copies of each nucleoporin and 10 Dyn2 molecules. Although Nup82, Nup159, and Nsp1 all contain α-helical domains predicted to form coiled-coil dimers, electron microscopy showed that the complex didn’t adopt an extended, rod-like conformation. Instead, the complex was shaped like the letter P, whose globular head domain was formed by the C-terminal coils of Nup159 and Nsp1 packed together with the entirety of Nup82. The structure’s tail consisted of Nup159’s N-terminal domains bound to Dyn2.
Fitting the Nup82 complex’s structure into a map of the entire NPC suggested that the FG repeats of Nup159 and Nsp1 could be oriented toward the pore’s central channel, where they would interact with transport factors moving through the pore. At the same time, Nup159’s N-terminal β-propeller domain would be exposed to the cytoplasm, allowing it to recruit the RNA helicase Dbp5 to disassemble messenger RNPs once they arrive in the cytoplasm.
Text by Ben Short