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Structure paper

TitleStructural transitions in kinesin minus-end directed microtubule motility.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateJul 29, 2024
AuthorsSatoki Shibata / Matthew Y Wang / Tsuyoshi Imasaki / Hideki Shigematsu / Yuanyuan Wei / Chacko Jobichen / Hajime Hagio / J Sivaraman / Sharyn A Endow / Ryo Nitta /
PubMed AbstractKinesin motor proteins hydrolyze ATP to produce force for spindle assembly and vesicle transport, performing essential functions in cell division and motility, but the structural changes required for ...Kinesin motor proteins hydrolyze ATP to produce force for spindle assembly and vesicle transport, performing essential functions in cell division and motility, but the structural changes required for force generation are uncertain. We now report high-resolution structures showing new transitions in the kinesin mechanochemical cycle, including power stroke fluctuations upon ATP binding and a post-hydrolysis state with bound ADP + free phosphate. We find that rate-limiting ADP release occurs upon microtubule binding, accompanied by central β-sheet twisting, which triggers the power stroke - stalk rotation and neck mimic docking - upon ATP binding. Microtubule release occurs with β-strand-to-loop transitions, implying that β-strand refolding induces Pi release and the recovery stroke. The strained β-sheet during the power stroke and strand-to-loop transitions identify the β-sheet as the long-sought motor spring.
External linksbioRxiv / PubMed:39131399 / PubMed Central
MethodsEM (helical sym.)
Resolution3.24 - 4.02 Å
Structure data

39664

8yy2

EMDB-39664, PDB-8yy2:
Kinesin-14 in nucleotide-free state bound to 13 PF Microtubule
Method: EM (helical sym.) / Resolution: 3.6 Å

39665

8yy3

EMDB-39665, PDB-8yy3:
Kinesin-14 in nucleotide-free state bound to 14 PF Microtubule
Method: EM (helical sym.) / Resolution: 3.24 Å

39666

8yy4

EMDB-39666, PDB-8yy4:
Kinesin-14 with AlF3 bound to 13 PF Microtubule
Method: EM (helical sym.) / Resolution: 4.02 Å

39667

8yy5

EMDB-39667, PDB-8yy5:
Kinesin-14 with AlF3 bound to 14 PF Microtubule
Method: EM (helical sym.) / Resolution: 3.99 Å

EMDB-39668: Kinesin-14 with AMPPNP bound to 13 PF Microtubule
Method: EM (helical sym.) / Resolution: 3.88 Å

EMDB-39669: Kinesin-14 with AMPPNP bound to 14 PF Microtubule
Method: EM (helical sym.) / Resolution: 3.6 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

Source
  • sus scrofa (pig)
  • drosophila melanogaster (fruit fly)
  • Drosophila melanogaster
KeywordsCELL CYCLE / Kinesin Motor Proteins / Force Production / Power Stroke Fluctuations / Motor Spring-like Element / Reversed Motility / Mechanochemical Coupling / Mechanical States

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