Characterization of the binding mode of JNK-interacting protein 1 (JIP1) to kinesin-light chain 1 (KLC1) - I2BC Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2018

Characterization of the binding mode of JNK-interacting protein 1 (JIP1) to kinesin-light chain 1 (KLC1)

Résumé

JIP1 was first identified as scaffold protein for the MAP kinase JNK and is a cargo protein for the kinesin1 molecular motor. JIP1 plays significant and broad roles in neurons, mainly as a regulator of kinesin1-dependent transport, and is associated with human pathologies such as cancer and Alzheimer disease. JIP1 is specifically recruited by the kinesin-light chain 1 (KLC1) of kinesin1, but the details of this interaction are not yet fully elucidated. Here, using calorimetry, we extensively biochemically characterized the interaction between KLC1 and JIP1. Using various truncated fragments of the tetratricopeptide repeat (TPR) domain of KLC1, we narrowed down its JIP1-binding region and identified seven KLC1 residues critical for JIP1 binding. These ITC-based binding data enabled us to footprint the JIP1-binding site on KLC1-TPR. This footprint was used to uncover the structural basis for the marginal inhibition of JIP1 binding by the autoinhibitory LFP-acidic motif of KLC1, as well as for the competition between JIP1 and another cargo protein of kinesin1, the W-acidic motif-containing Alcadein-α. Also, we examined the role of each of these critical residues of KLC1 for JIP1 binding in the light of the previously reported crystal structure of the KLC1-TPR:JIP1 complex. Finally, sequence search in eukaryotic genomes identified several proteins, among which SH2D6 that exhibit similar motif to the KLC1-binding motif of JIP1. Overall, our extensive biochemical characterization of the KLC:JIP1 interaction, as well as identification of potential KLC1-binding partners improve the understanding of how this growing family of cargos is recruited to kinesin1 by KLC1.

Dates et versions

hal-02183096 , version 1 (15-07-2019)

Identifiants

Citer

T. Quyen Nguyen, Magali Aumont-Niçaise, Jessica Andreani, Christophe Velours, Mélanie Chenon, et al.. Characterization of the binding mode of JNK-interacting protein 1 (JIP1) to kinesin-light chain 1 (KLC1). Journal of Biological Chemistry, 2018, 293 (36), pp.13946--13960. ⟨10.1074/jbc.RA118.003916⟩. ⟨hal-02183096⟩
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