4bl6

Publication Abstract from PubMed

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 A 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.

Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein.,Liu Y, Salter HK, Holding AN, Johnson CM, Stephens E, Lukavsky PJ, Walshaw J, Bullock SL Genes Dev. 2013 Jun 1;27(11):1233-46. doi: 10.1101/gad.212381.112. Epub 2013 May , 30. PMID:23723415^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.