Molecular mechanism of cytoplasmic dynein tension sensing

Lu Rao, Florian Berger, Matthew P. Nicholas, Arne Gennerich

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cytoplasmic dynein is the most complex cytoskeletal motor protein and is responsible for numerous biological functions. Essential to dynein’s function is its capacity to respond anisotropically to tension, so that its microtubule-binding domains bind microtubules more strongly when under backward load than forward load. The structural mechanisms by which dynein senses directional tension, however, are unknown. Using a combination of optical tweezers, mutagenesis, and chemical cross-linking, we show that three structural elements protruding from the motor domain—the linker, buttress, and stalk—together regulate directional tension-sensing. We demonstrate that dynein’s anisotropic response to directional tension is mediated by sliding of the coiled-coils of the stalk, and that coordinated conformational changes of dynein’s linker and buttress control this process. We also demonstrate that the stalk coiled-coils assume a previously undescribed registry during dynein’s stepping cycle. We propose a revised model of dynein’s mechanochemical cycle which accounts for our findings.

Original languageEnglish (US)
Article number3332
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Cytoplasmic Dyneins
Dyneins
coils
mutagenesis
Microtubules
cycles
Optical Tweezers
Optical tweezers
sliding
Mutagenesis
Cytoskeletal Proteins
proteins
Registries

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Molecular mechanism of cytoplasmic dynein tension sensing. / Rao, Lu; Berger, Florian; Nicholas, Matthew P.; Gennerich, Arne.

In: Nature Communications, Vol. 10, No. 1, 3332, 01.12.2019.

Research output: Contribution to journalArticle

Rao, Lu ; Berger, Florian ; Nicholas, Matthew P. ; Gennerich, Arne. / Molecular mechanism of cytoplasmic dynein tension sensing. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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