TY - JOUR T1 - Coiled-coil registry shifts in the F684I mutant of Bicaudal result in cargo-independent activation of dynein motility JF - bioRxiv DO - 10.1101/776187 SP - 776187 AU - Heying Cui AU - Kathleen M. Trybus AU - M. Yusuf Ali AU - Puja Goyal AU - Kaiqi Zhang AU - Jia Ying Loh AU - Sozanne R. Solmaz Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/29/776187.abstract N2 - 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. ER -