The light chains of kinesin-1 are autoinhibited

Yan Y Yip, Stefano Pernigo, Anneri Sanger, Mengjia Xu, Maddy Parsons, Roberto A Steiner, Mark P Dodding

Research output: Contribution to journalArticle (Academic Journal)peer-review

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The light chains (KLCs) of the microtubule motor kinesin-1 bind cargoes and regulate its activity. Through their tetratricopeptide repeat domain (KLC(TPR)), they can recognize short linear peptide motifs found in many cargo proteins characterized by a central tryptophan flanked by aspartic/glutamic acid residues (W-acidic). Using a fluorescence resonance energy transfer biosensor in combination with X-ray crystallographic, biochemical, and biophysical approaches, we describe how an intramolecular interaction between the KLC2(TPR) domain and a conserved peptide motif within an unstructured region of the molecule, partly occludes the W-acidic binding site on the TPR domain. Cargo binding displaces this interaction, effecting a global conformational change in KLCs resulting in a more extended conformation. Thus, like the motor-bearing kinesin heavy chains, KLCs exist in a dynamic conformational state that is regulated by self-interaction and cargo binding. We propose a model by which, via this molecular switch, W-acidic cargo binding regulates the activity of the holoenzyme.

Original languageEnglish
Pages (from-to)2418-2423
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
Early online date16 Feb 2016
Publication statusPublished - Mar 2016


  • Amino Acid Sequence
  • Humans
  • Kinesin
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Journal Article
  • Research Support, Non-U.S. Gov't

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