6EJN

The KLC2 TPR domain bound to the JIP3 leucine zipper domain

6EJN の概要

• エントリーDOI: 10.2210/pdb6ejn/pdb
• 分子名称: Kinesin light chain 2, C-Jun-amino-terminal kinase-interacting protein 3 (2 entities in total)
• 機能のキーワード: kinesin jip3 transport cargo molecular motor, transport protein
• 由来する生物種: Mus musculus (House Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82720.10

構造登録者

Cockburn, J.,Hesketh, S.J.,Way, M. (登録日: 2017-09-22, 公開日: 2018-09-05, 最終更新日: 2024-01-17)

主引用文献

Cockburn, J.J.B.,Hesketh, S.J.,Mulhair, P.,Thomsen, M.,O'Connell, M.J.,Way, M.
Insights into Kinesin-1 Activation from the Crystal Structure of KLC2 Bound to JIP3.
Structure, 26:1486-1498.e6, 2018

PubMed Abstract: Kinesin-1 transports numerous cellular cargoes along microtubules. The kinesin-1 light chain (KLC) mediates cargo binding and regulates kinesin-1 motility. To investigate the molecular basis for kinesin-1 recruitment and activation by cargoes, we solved the crystal structure of the KLC2 tetratricopeptide repeat (TPR) domain bound to the cargo JIP3. This, combined with biophysical and molecular evolutionary analyses, reveals a kinesin-1 cargo binding site, located on KLC TPR1, which is conserved in homologs from sponges to humans. In the complex, JIP3 crosslinks two KLC2 TPR domains via their TPR1s. We show that TPR1 forms a dimer interface that mimics JIP3 binding in all crystal structures of the unbound KLC TPR domain. We propose that cargo-induced dimerization of the KLC TPR domains via TPR1 is a general mechanism for activating kinesin-1. We relate this to activation by tryptophan-acidic cargoes, explaining how different cargoes activate kinesin-1 through related molecular mechanisms.

PubMed: 30197037
DOI: 10.1016/j.str.2018.07.011

実験手法

X-RAY DIFFRACTION (3.2 Å)