Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

Joseph Atherton, Irene Farabella, I. Mei Yu, Steven S. Rosenfeld, Anne Houdusse, Maya Topf, Carolyn A. Moores

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles--including their nucleotide-free states--at ∼ 7 Å resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin-microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface.

Original languageEnglish (US)
Article numbere03680
Pages (from-to)e03680
JournaleLife
Volume3
DOIs
StatePublished - 2014

Keywords

  • ATPase
  • biophysics
  • cryo-electron microscopy
  • cytoskeleton
  • human
  • kinesin
  • microtubule
  • motor
  • structural biology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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