5FJY

Crystal structure of mouse kinesin light chain 2 (residues 161-480)

Summary for 5FJY

• Entry DOI: 10.2210/pdb5fjy/pdb
• Descriptor: KINESIN LIGHT CHAIN 2, UNKNOWN PEPTIDE (2 entities in total)
• Functional Keywords: protein transport, molecular transport, tpr domains, autoinhibition
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Total number of polymer chains: 6
• Total formula weight: 110443.57

Authors

Pernigo, S.,Yip, Y.Y.,Sanger, A.,Xu, M.,Dodding, M.P.,Steiner, R.A. (deposition date: 2015-10-14, release date: 2016-02-24, Last modification date: 2024-10-16)

Primary citation

Yip, Y.Y.,Pernigo, S.,Sanger, A.,Xu, M.,Parsons, M.,Steiner, R.A.,Dodding, M.P.
The Light Chains of Kinesin-1 are Autoinhibited.
Proc.Natl.Acad.Sci.USA, 113:2418-, 2016

PubMed Abstract: 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.

PubMed: 26884162
DOI: 10.1073/PNAS.1520817113

Experimental method

X-RAY DIFFRACTION (4 Å)