Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors

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 recogn...

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Main Authors: Stefano Pernigo, Magda S Chegkazi, Yan Y Yip, Conor Treacy, Giulia Glorani, Kjetil Hansen, Argyris Politis, Soi Bui, Mark P Dodding, Roberto A Steiner
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/38362
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author Stefano Pernigo
Magda S Chegkazi
Yan Y Yip
Conor Treacy
Giulia Glorani
Kjetil Hansen
Argyris Politis
Soi Bui
Mark P Dodding
Roberto A Steiner
author_facet Stefano Pernigo
Magda S Chegkazi
Yan Y Yip
Conor Treacy
Giulia Glorani
Kjetil Hansen
Argyris Politis
Soi Bui
Mark P Dodding
Roberto A Steiner
author_sort Stefano Pernigo
collection DOAJ
description 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.
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spelling doaj.art-a58fc294a3834a8bbed2b1ec3afd638c2022-12-22T04:29:20ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.38362Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptorsStefano Pernigo0Magda S Chegkazi1https://orcid.org/0000-0002-0855-2681Yan Y Yip2Conor Treacy3Giulia Glorani4Kjetil Hansen5https://orcid.org/0000-0002-0085-8440Argyris Politis6https://orcid.org/0000-0002-6658-3224Soi Bui7Mark P Dodding8https://orcid.org/0000-0001-8091-6534Roberto A Steiner9https://orcid.org/0000-0001-7084-9745Randall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomDepartment of Chemistry, King’s College London, London, United KingdomDepartment of Chemistry, King’s College London, London, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom; School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, United KingdomRandall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, United KingdomThe 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.https://elifesciences.org/articles/38362molecular motorkinesin-1X-ray crystallography
spellingShingle Stefano Pernigo
Magda S Chegkazi
Yan Y Yip
Conor Treacy
Giulia Glorani
Kjetil Hansen
Argyris Politis
Soi Bui
Mark P Dodding
Roberto A Steiner
Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
eLife
molecular motor
kinesin-1
X-ray crystallography
title Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
title_full Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
title_fullStr Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
title_full_unstemmed Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
title_short Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors
title_sort structural basis for isoform specific kinesin 1 recognition of y acidic cargo adaptors
topic molecular motor
kinesin-1
X-ray crystallography
url https://elifesciences.org/articles/38362
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