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

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

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Received: 4 March 2013; in revised form: 10 May 2013 / Accepted: 4 June 2013 / Published: 17 June 2013
(This article belongs to the Special Issue Protein Folding 2015)
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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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA 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. International Journal of Molecular Sciences. 2013; 14(6):12675-12695.

Chicago/Turabian Style

Azoulay, Itzhaq; Kucherenko, Nataly; Nachliel, Esther; Gutman, Menachem; Azem, Abdussalam; Tsfadia, Yossi. 2013. "Tracking the Interplay between Bound Peptide and the Lid Domain of DnaK, Using Molecular Dynamics." Int. J. Mol. Sci. 14, no. 6: 12675-12695.


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