Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility.

Autor: Cui H; Department of Chemistry, State University of New York at Binghamton, Binghamton, New York, USA., Ali MY; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA., Goyal P; Department of Chemistry, State University of New York at Binghamton, Binghamton, New York, USA., Zhang K; Department of Chemistry, State University of New York at Binghamton, Binghamton, New York, USA., Loh JY; Department of Chemistry, State University of New York at Binghamton, Binghamton, New York, USA., Trybus KM; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA., Solmaz SR; Department of Chemistry, State University of New York at Binghamton, Binghamton, New York, USA.
Jazyk: angličtina
Zdroj: Traffic (Copenhagen, Denmark) [Traffic] 2020 Jul; Vol. 21 (7), pp. 463-478.
DOI: 10.1111/tra.12734
Abstrakt: 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.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje