title: Structural basis for microtubule binding and release by dynein.
abstract: Cytoplasmic dynein is a microtubule-based motor required for intracellular transport and cell division. Its movement involves coupling cycles of track binding and release with cycles of force-generating nucleotide hydrolysis. How this is accomplished given the ~25 nanometers separating dynein's track- and nucleotide-binding sites is not understood. Here, we present a subnanometer-resolution structure of dynein's microtubule-binding domain bound to microtubules by cryo-electron microscopy that was used to generate a pseudo-atomic model of the complex with molecular dynamics. We identified large rearrangements triggered by track binding and specific interactions, confirmed by mutagenesis and single-molecule motility assays, which tune dynein's affinity for microtubules. Our results provide a molecular model for how dynein's binding to microtubules is communicated to the rest of the motor.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, United States.|Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Redwine
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, United States.
authors.forename: R
authors.initials: R
authors.lastname: Hernandez-Lopez
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zou
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Reck-Peterson
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, United States.
authors.forename: A E
authors.initials: AE
authors.lastname: Leschziner
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D056445:Cytoplasmic Dyneins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016296:Mutagenesis; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D056445:Cytoplasmic Dyneins