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

Stefano Pernigo, Magda S Chegkazi, Yan Y Yip, Conor Treacy, Giulia Glorani, Kjetil Hansen, Argyris Politis, Soi Bui, Mark P Dodding, Roberto A Steiner

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

5 Citations (Scopus)
239 Downloads (Pure)

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.
Original languageEnglish
Article numbere38362
JournaleLife
Volume7
DOIs
Publication statusPublished - 16 Oct 2018

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