Next Article in Journal
Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins
Next Article in Special Issue
Reinvestigation of the Oxidative Folding Pathways of Hen Egg White Lysozyme: Switching of the Major Pathways by Temperature Control
Previous Article in Journal
Design, Synthesis, Biological Activity and Molecular Dynamics Studies of Specific Protein Tyrosine Phosphatase 1B Inhibitors over SHP-2
Previous Article in Special Issue
Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2013, 14(6), 12675-12695; doi:10.3390/ijms140612675

Tracking the Interplay between Bound Peptide and the Lid Domain of DnaK, Using Molecular Dynamics

Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
*
Author to whom correspondence should be addressed.
Received: 4 March 2013 / Revised: 10 May 2013 / Accepted: 4 June 2013 / Published: 17 June 2013
(This article belongs to the collection Protein Folding)
View Full-Text   |   Download PDF [772 KB, uploaded 19 June 2014]   |  

Abstract

Hsp70 chaperones consist of two functional domains: the 44 kDa Nucleotide Binding Domain (NBD), that binds and hydrolyses ATP, and the 26 kDa Substrate Binding Domain (SBD), which binds unfolded proteins and reactivates them, utilizing energy obtained from nucleotide hydrolysis. The structure of the SBD of the bacterial Hsp70, DnaK, consists of two sub-domains: A β-sandwich part containing the hydrophobic cavity to which the hepta-peptide NRLLLTG (NR) is bound, and a segment made of 5 α-helices, called the “lid” that caps the top of the β-sandwich domain. In the present study we used the Escherichia coli Hsp70, DnaK, as a model for Hsp70 proteins, focusing on its SBD domain, examining the changes in the lid conformation. We deliberately decoupled the NBD from the SBD, limiting the study to the structure of the SBD section, with an emphasis on the interaction between the charges of the peptide with the residues located in the lid. Molecular dynamics simulations of the complex revealed significant mobility within the lid structure; as the structure was released from the forces operating during the crystallization process, the two terminal helices established a contact with the positive charge at the tip of the peptide. This contact is manifested only in the presence of electrostatic attraction. The observed internal motions within the lid provide a molecular role for the function of this sub-domain during the reaction cycle of Hsp 70 chaperones.
Keywords: Hsp 70 chaperone; DnaK; reaction mechanism; molecular dynamics Hsp 70 chaperone; DnaK; reaction mechanism; molecular dynamics
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Azoulay, I.; Kucherenko, N.; Nachliel, E.; Gutman, M.; Azem, A.; Tsfadia, Y. Tracking the Interplay between Bound Peptide and the Lid Domain of DnaK, Using Molecular Dynamics. Int. J. Mol. Sci. 2013, 14, 12675-12695.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top