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

Genes Dev. 2013 Jun 1;27(11):1233-46. doi: 10.1101/gad.212381.112. Epub 2013 May 30.


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.

Keywords: Bicaudal-D; Drosophila.; cargo binding; coiled coil; crystal structure; dynein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / chemistry*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Dyneins / chemistry
  • Dyneins / metabolism*
  • Genes, Dominant
  • Models, Biological
  • Models, Molecular
  • Mutation / genetics
  • Protein Binding
  • Structure-Activity Relationship
  • rab GTP-Binding Proteins / metabolism


  • BicD protein, Drosophila
  • Drosophila Proteins
  • Rab6 protein
  • egl protein, Drosophila
  • Dyneins
  • rab GTP-Binding Proteins