TY - JOUR T1 - Coil-to-Helix Transition at the Nup358-BicD2 Interface for Dynein Recruitment and Activation JF - bioRxiv DO - 10.1101/2021.05.06.443034 SP - 2021.05.06.443034 AU - James M. Gibson AU - Heying Cui AU - M. Yusuf Ali AU - Xiaoxin Zhao AU - Erik W. Debler AU - Jing Zhao AU - Kathleen M. Trybus AU - Sozanne R. Solmaz AU - Chunyu Wang Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/07/2021.05.06.443034.abstract N2 - Nup358, a nuclear pore protein, facilitates a nuclear positioning pathway that is essential for brain development. Nup358 binds and activates the auto-inhibited dynein adaptor Bicaudal D2 (BicD2), which in turn recruits and activates the dynein machinery to position the nucleus. The molecular details of the Nup358/BicD2 interaction remain poorly understood. Here, we show that a minimal dimerized Nup358 domain activates dynein/dynactin/BicD2 for processive motility on microtubules. Using nuclear magnetic resonance (NMR) titration and chemical exchange saturation transfer (CEST), a Nup358-helix encompassing residues 2162-2184 was identified, which transitioned from random coil to an a-helix 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 the cargo adaptor Nup358 though a “cargo recognition α-helix”, a structural feature that may stabilize BicD2 in its activated state, promoting activation of dynein motility.Competing Interest StatementThe authors have declared no competing interest. ER -