4BL6

Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to co-ordinate recruitment of cargos to dynein

Summary for 4BL6

• Entry DOI: 10.2210/pdb4bl6/pdb
• Descriptor: PROTEIN BICAUDAL D, ARGININE (3 entities in total)
• Functional Keywords: protein transport, cargo binding
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY)
• Cellular location: Cytoplasm, cytoskeleton : P16568
• Total number of polymer chains: 4
• Total formula weight: 45199.23

Authors

Liu, Y.,Salter, H.K.,Holding, A.N.,Johnson, C.M.,Stephens, E.,Lukavsky, P.J.,Walshaw, J.,Bullock, S.L. (deposition date: 2013-05-02, release date: 2013-06-12, Last modification date: 2024-11-13)

Primary citation

Liu, Y.,Salter, H.K.,Holding, A.N.,Johnson, C.M.,Stephens, E.,Lukavsky, P.J.,Walshaw, J.,Bullock, S.L.
Bicaudal-D Uses a Parallel, Homodimeric Coiled Coil with Heterotypic Registry to Coordinate Recruitment of Cargos to Dynein
Genes Dev., 27:1233-, 2013

PubMed Abstract: Cytoplasmic dynein is the major minus end-directed microtubule motor in eukaryotes. However, there is little structural insight into how different cargos are recognized and linked to the motor complex. Here we describe the 2.2 Å resolution crystal structure of a cargo-binding region of the dynein adaptor Bicaudal-D (BicD), which reveals a parallel coiled-coil homodimer. We identify a shared binding site for two cargo-associated proteins-Rab6 and the RNA-binding protein Egalitarian (Egl)-within a region of the BicD structure with classical, homotypic core packing. Structure-based mutagenesis in Drosophila provides evidence that occupancy of this site drives association of BicD with dynein, thereby coupling motor recruitment to cargo availability. The structure also contains a region in which, remarkably, the same residues in the polypeptide sequence have different heptad registry in each chain. In vitro and in vivo analysis of a classical Drosophila dominant mutation reveals that this heterotypic region regulates the recruitment of dynein to BicD. Our results support a model in which the heterotypic segment is part of a molecular switch that promotes release of BicD autoinhibition following cargo binding to the neighboring, homotypic coiled-coil region. Overall, our data reveal a pivotal role of a highly asymmetric coiled-coil domain in coordinating the assembly of cargo-motor complexes.

PubMed: 23723415
DOI: 10.1101/GAD.212381.112

Experimental method

X-RAY DIFFRACTION (2.18 Å)