TY - JOUR TI - Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment AU - Gibson, James M AU - Cui, Heying AU - Ali, M Yusuf AU - Zhao, Xiaoxin AU - Debler, Erik W AU - Zhao, Jing AU - Trybus, Kathleen M AU - Solmaz, Sozanne R AU - Wang, Chunyu A2 - Carter, Andrew P A2 - Akhmanova, Anna VL - 11 PY - 2022 DA - 2022/03/01 SP - e74714 C1 - eLife 2022;11:e74714 DO - 10.7554/eLife.74714 UR - https://doi.org/10.7554/eLife.74714 AB - Nup358, a protein of the nuclear pore complex, facilitates a nuclear positioning pathway that is essential for many biological processes, including neuromuscular and brain development. Nup358 interacts with the dynein adaptor Bicaudal D2 (BicD2), which in turn recruits the dynein machinery to position the nucleus. However, the molecular mechanisms of the Nup358/BicD2 interaction and the activation of transport remain poorly understood. Here for the first time, we show that a minimal Nup358 domain activates dynein/dynactin/BicD2 for processive motility on microtubules. Using nuclear magnetic resonance titration and chemical exchange saturation transfer, mutagenesis, and circular dichroism spectroscopy, a Nup358 α-helix encompassing residues 2162–2184 was identified, which transitioned from a random coil to an α-helical conformation upon BicD2 binding and formed the core of the Nup358-BicD2 interface. Mutations in this region of Nup358 decreased the Nup358/BicD2 interaction, resulting in decreased dynein recruitment and impaired motility. BicD2 thus recognizes Nup358 through a ‘cargo recognition α-helix,’ a structural feature that may stabilize BicD2 in its activated state and promote processive dynein motility. KW - bidirectional transport KW - dynein KW - nuclear positioning KW - NMR KW - TIRF KW - BicD2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -