6TZW

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

Summary for 6TZW

• Entry DOI: 10.2210/pdb6tzw/pdb
• Descriptor: Protein bicaudal D, CALCIUM ION (3 entities in total)
• Functional Keywords: dynein, adaptor, bicaudal, bicd, coiled coil, registry shift, coiled-coil, microtubules, dynein adaptor, cargo recognition, cytoskeletal motor, auto-inhibition, golgi, nucleus, nuclear positioning, transport, intracellular tranpsort, nup358, motor protein
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 22015.10

Authors

Cui, H.,Solmaz, S.R. (deposition date: 2019-08-13, release date: 2020-05-13, Last modification date: 2023-10-11)

Primary citation

Cui, H.,Ali, M.Y.,Goyal, P.,Zhang, K.,Loh, J.Y.,Trybus, K.M.,Solmaz, S.R.
Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility.
Traffic, 21:463-478, 2020

PubMed 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.

PubMed: 32378283
DOI: 10.1111/tra.12734

Experimental method

X-RAY DIFFRACTION (2.35 Å)