6tzw
From Proteopedia
Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility
Structural highlights
FunctionBICD_DROME This protein is essential for differentiation. It may play a role in localizing of Nanos (a maternal determinant) activity in oocytes. BicD mutations cause Nanos mislocalization and thus bicaudal development. Publication Abstract from PubMedThe 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. This article is protected by copyright. All rights reserved. Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility.,Cui H, Ali MY, Goyal P, Zhang K, Loh JY, Trybus KM, Solmaz SR Traffic. 2020 May 7. doi: 10.1111/tra.12734. PMID:32378283[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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