PT  - JOURNAL ARTICLE
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
TI  - Coil-to-Helix Transition at the Nup358-BicD2 Interface for Dynein Recruitment and Activation
AID  - 10.1101/2021.05.06.443034
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.06.443034
4099  - http://biorxiv.org/content/early/2021/05/07/2021.05.06.443034.short
4100  - http://biorxiv.org/content/early/2021/05/07/2021.05.06.443034.full
AB  - 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.