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Magic-angle-spinning NMR structure of the kinesin-1 motor domain assembled with microtubules reveals the elusive neck linker orientation

Author

Listed:
  • Chunting Zhang

    (University of Delaware)

  • Changmiao Guo

    (University of Delaware)

  • Ryan W. Russell

    (University of Delaware)

  • Caitlin M. Quinn

    (University of Delaware)

  • Mingyue Li

    (University of Delaware)

  • John C. Williams

    (Beckman Research Institute of City of Hope)

  • Angela M. Gronenborn

    (University of Pittsburgh School of Medicine
    University of Pittsburgh School of Medicine)

  • Tatyana Polenova

    (University of Delaware
    University of Pittsburgh School of Medicine)

Abstract

Microtubules (MTs) and their associated proteins play essential roles in maintaining cell structure, organelle transport, cell motility, and cell division. Two motors, kinesin and cytoplasmic dynein link the MT network to transported cargos using ATP for force generation. Here, we report an all-atom NMR structure of nucleotide-free kinesin-1 motor domain (apo-KIF5B) in complex with paclitaxel-stabilized microtubules using magic-angle-spinning (MAS) NMR spectroscopy. The structure reveals the position and orientation of the functionally important neck linker and how ADP induces structural and dynamic changes that ensue in the neck linker. These results demonstrate that the neck linker is in the undocked conformation and oriented in the direction opposite to the KIF5B movement. Chemical shift perturbations and intensity changes indicate that a significant portion of ADP-KIF5B is in the neck linker docked state. This study also highlights the unique capability of MAS NMR to provide atomic-level information on dynamic regions of biological assemblies.

Suggested Citation

  • Chunting Zhang & Changmiao Guo & Ryan W. Russell & Caitlin M. Quinn & Mingyue Li & John C. Williams & Angela M. Gronenborn & Tatyana Polenova, 2022. "Magic-angle-spinning NMR structure of the kinesin-1 motor domain assembled with microtubules reveals the elusive neck linker orientation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34026-w
    DOI: 10.1038/s41467-022-34026-w
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    Cited by:

    1. Agnes Adler & Mamata Bangera & J. Wouter Beugelink & Salima Bahri & Hugo Ingen & Carolyn A. Moores & Marc Baldus, 2024. "A structural and dynamic visualization of the interaction between MAP7 and microtubules," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Changmiao Guo & Raymundo Alfaro-Aco & Chunting Zhang & Ryan W. Russell & Sabine Petry & Tatyana Polenova, 2023. "Structural basis of protein condensation on microtubules underlying branching microtubule nucleation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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