Cui, H., Ali, M.Y., Goyal, P., Zhang, K., Loh, J.Y., Trybus, K.M., Solmaz, S.R. (2020). Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility. Traffic 21(7): 463--478.
FlyBase ID
FBrf0246069
Publication Type
Research paper
Abstract
The dynein adaptor Drosophila Bicaudal D (BicD) is auto-inhibited and activates dynein motility only after cargo is bound, but the underlying mechanism is elusive. In contrast, we show that the full-length BicD/F684I mutant activates dynein processivity even in the absence of cargo. Our X-ray structure of the C-terminal domain of the BicD/F684I mutant reveals a coiled-coil registry shift; in the N-terminal region, the two helices of the homodimer are aligned, whereas they are vertically shifted in the wild-type. One chain is partially disordered and this structural flexibility is confirmed by computations, which reveal that the mutant transitions back and forth between the two registries. We propose that a coiled-coil registry shift upon cargo-binding activates BicD for dynein recruitment. Moreover, the human homolog BicD2/F743I exhibits diminished binding of cargo adaptor Nup358, implying that a coiled-coil registry shift may be a mechanism to modulate cargo selection for BicD2-dependent transport pathways.
