Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
- King's College London, United Kingdom
Abstract
The light chains (KLCs) of the heterotetrameric microtubule motor kinesin-1, that bind to cargo adaptor proteins and regulate its activity, have a capacity to recognize short peptides via their tetratricopeptide repeat domains (KLCTPR). Here, using X-ray crystallography, we show how kinesin-1 recognizes a novel class of adaptor motifs that we call 'Y-acidic' (tyrosine flanked by acidic residues), in a KLC-isoform specific manner. Binding specificities of Y-acidic motifs (present in JIP1 and in TorsinA) to KLC1TPR are distinct from those utilized for the recognition of W-acidic motifs found in adaptors that are KLC- isoform non-selective. However, a partial overlap on their receptor binding sites implies that adaptors relying on Y-acidic and W-acidic motifs must act independently. We propose a model to explain why these two classes of motifs that bind to the concave surface of KLCTPR with similar low micromolar affinity can exhibit different capacities to promote kinesin-1 activity.
Data availability
Diffraction data and coordinates are publicly available in PDB under the accession codes 6FUZ and 6FV0
Article and author information
Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/L006774/1)
- Soi Bui
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Samara L Reck-Peterson, University of California, San Diego, United States
Publication history
- Received: May 14, 2018
- Accepted: October 14, 2018
- Accepted Manuscript published: October 15, 2018 (version 1)
- Version of Record published: November 2, 2018 (version 2)
- Version of Record updated: November 7, 2018 (version 3)
Copyright
© 2018, Pernigo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
eLife 7:e38362.
https://doi.org/10.7554/eLife.38362
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