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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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

Fingerprint

Kinesin
Conformations
Crystal structure
crystal structure
Neck
cargo
locomotion
adenosine triphosphate
nucleotides
resonance fluorescence
helices
energy transfer
Fluorescence Resonance Energy Transfer
cycles
Microtubules
Chemical elements
Adenosine Triphosphatases
Nucleotides
Adenosine Triphosphate
Head

All Science Journal Classification (ASJC) codes

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

Cite this

Guan, Ruifang ; Zhang, Lei ; Su, Qian Peter ; Mickolajczyk, Keith J. ; Chen, Geng Yuan ; Hancock, William O. ; Sun, Yujie ; Zhao, Yongfang ; Chen, Zhucheng. / Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin. In: Nature communications. 2017 ; Vol. 8.
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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.",
author = "Ruifang Guan and Lei Zhang and Su, {Qian Peter} and Mickolajczyk, {Keith J.} and Chen, {Geng Yuan} and Hancock, {William O.} and Yujie Sun and Yongfang Zhao and Zhucheng Chen",
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Guan, R, Zhang, L, Su, QP, Mickolajczyk, KJ, Chen, GY, Hancock, WO, Sun, Y, Zhao, Y & Chen, Z 2017, 'Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin', Nature communications, vol. 8, 14951. https://doi.org/10.1038/ncomms14951

Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin. / Guan, Ruifang; Zhang, Lei; Su, Qian Peter; Mickolajczyk, Keith J.; Chen, Geng Yuan; Hancock, William O.; Sun, Yujie; Zhao, Yongfang; Chen, Zhucheng.

In: Nature communications, Vol. 8, 14951, 10.04.2017.

Research output: Contribution to journalArticle

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T1 - Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin

AU - Guan, Ruifang

AU - Zhang, Lei

AU - Su, Qian Peter

AU - Mickolajczyk, Keith J.

AU - Chen, Geng Yuan

AU - Hancock, William O.

AU - Sun, Yujie

AU - Zhao, Yongfang

AU - Chen, Zhucheng

PY - 2017/4/10

Y1 - 2017/4/10

N2 - 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.

AB - 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.

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