title: Tension on the linker gates the ATP-dependent release of dynein from microtubules.
abstract: Cytoplasmic dynein is a dimeric motor that transports intracellular cargoes towards the minus end of microtubules (MTs). In contrast to other processive motors, stepping of the dynein motor domains (heads) is not precisely coordinated. Therefore, the mechanism of dynein processivity remains unclear. Here, by engineering the mechanical and catalytic properties of the motor, we show that dynein processivity minimally requires a single active head and a second inert MT-binding domain. Processivity arises from a high ratio of MT-bound to unbound time, and not from interhead communication. In addition, nucleotide-dependent microtubule release is gated by tension on the linker domain. Intramolecular tension sensing is observed in dynein's stepping motion at high interhead separations. On the basis of these results, we propose a quantitative model for the stepping characteristics of dynein and its response to chemical and mechanical perturbation.
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Cleary
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dewitt
authors.affiliation: Department of Physics, University of California, Berkeley, California 94720, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bilyard
authors.affiliation: Department of Physics, University of California, Berkeley, California 94720, USA.
authors.forename: Zaw Min
authors.initials: ZM
authors.lastname: Htet
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, California 94720, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Belyy
authors.affiliation: Department of Physics, University of California, Berkeley, California 94720, USA.
authors.forename: Danna D
authors.initials: DD
authors.lastname: Chan
authors.affiliation: Department of Physics, University of California, Berkeley, California 94720, USA.
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Chang
authors.affiliation: Department of Physics, University of California, Berkeley, California 94720, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Yildiz
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000737:chemistry*; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008870:Microtubules / Q000737:chemistry*; D009010:Monte Carlo Method; D009038:Motion; D009154:Mutation; D009711:Nucleotides / Q000737:chemistry / Q000235:genetics; D055095:Optics and Photonics; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012617:Sea Urchins; D013314:Stress, Mechanical; D013824:Thermus / Q000378:metabolism
chemical_list: D009711:Nucleotides; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D005982:Glutathione Transferase; D000251:Adenosine Triphosphatases; D004398:Dyneins
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