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Title: Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms

Abstract

Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove butmore » not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.« less

Authors:
; ; ; ; ; ; ; ; ;  [1];  [2];  [2]
  1. (SGC-Toronto)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGN
OSTI Identifier:
1044419
Resource Type:
Journal Article
Journal Name:
PLoS One
Additional Journal Information:
Journal Volume: 7; Journal Issue: (3) ; 03, 2012
Country of Publication:
United States
Language:
ENGLISH
Subject:
08 HYDROGEN; ASPARAGINE; CALORIMETRY; CARGO; CHAINS; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; HEAT-SHOCK PROTEINS; HYDROGEN; ORGANIZING; PROTEINS; RESIDUES; TITRATION

Citation Formats

Zhu, Haizhong, Lee, Han Youl, Tong, Yufeng, Hong, Bum-Soo, Kim, Kyung-Phil, Shen, Yang, Lim, Kyung Jik, Mackenzie, Farrell, Tempel, Wolfram, Park, Hee-Won, PPCS), and Toronto). Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms. United States: N. p., 2012. Web. doi:10.1371/journal.pone.0033943.
Zhu, Haizhong, Lee, Han Youl, Tong, Yufeng, Hong, Bum-Soo, Kim, Kyung-Phil, Shen, Yang, Lim, Kyung Jik, Mackenzie, Farrell, Tempel, Wolfram, Park, Hee-Won, PPCS), & Toronto). Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms. United States. doi:10.1371/journal.pone.0033943.
Zhu, Haizhong, Lee, Han Youl, Tong, Yufeng, Hong, Bum-Soo, Kim, Kyung-Phil, Shen, Yang, Lim, Kyung Jik, Mackenzie, Farrell, Tempel, Wolfram, Park, Hee-Won, PPCS), and Toronto). Tue . "Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms". United States. doi:10.1371/journal.pone.0033943.
@article{osti_1044419,
title = {Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms},
author = {Zhu, Haizhong and Lee, Han Youl and Tong, Yufeng and Hong, Bum-Soo and Kim, Kyung-Phil and Shen, Yang and Lim, Kyung Jik and Mackenzie, Farrell and Tempel, Wolfram and Park, Hee-Won and PPCS) and Toronto)},
abstractNote = {Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.},
doi = {10.1371/journal.pone.0033943},
journal = {PLoS One},
number = (3) ; 03, 2012,
volume = 7,
place = {United States},
year = {2012},
month = {10}
}