6tzw

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

spinqualitylabelsall models 6tzw, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tzw is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BICD_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 PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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