Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin

Ruifang Guan, Lei Zhang, Qian Peter Su, Keith J. Mickolajczyk, Geng Yuan Chen, William O. Hancock, Yujie Sun, Yongfang Zhao, Zhucheng Chen

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Abstract

Kinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding α6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension. The backward-docked structure of NIS is essential for motility of the motor. Our findings reveal a key missing conformation of kinesins, which provides the structural basis of the stable 2HB state and offers a tension-based rationale for an optimal NL length to ensure processivity of the motor.

Original languageEnglish (US)
Article number14951
JournalNature communications
Volume8
DOIs
StatePublished - Apr 10 2017

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All Science Journal Classification (ASJC) codes

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

Cite this

Guan, R., Zhang, L., Su, Q. P., Mickolajczyk, K. J., Chen, G. Y., Hancock, W. O., Sun, Y., Zhao, Y., & Chen, Z. (2017). Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin. Nature communications, 8, [14951]. https://doi.org/10.1038/ncomms14951