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

Nat Commun. 2017 Apr 10:8:14951. doi: 10.1038/ncomms14951.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoproteins / chemistry*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / metabolism
  • Crystallography, X-Ray
  • Drosophila
  • Fluorescence Resonance Energy Transfer
  • Kinesins / chemistry*
  • Kinesins / metabolism
  • Models, Molecular
  • Nucleotides / chemistry
  • Protein Conformation
  • Rats
  • Staining and Labeling

Substances

  • Apoproteins
  • Caenorhabditis elegans Proteins
  • Nucleotides
  • ZEN-4 protein, C elegans
  • Kinesins