Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.

Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD) modulate substrate recognition at...

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Autores principales:	Federica Chiappori, Ivan Merelli, Giorgio Colombo, Luciano Milanesi, Giulia Morra
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/60fe7b6c3bd94dd8b27a678145948046
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spelling	oai:doaj.org-article:60fe7b6c3bd94dd8b27a6781459480462021-11-18T05:52:34ZMolecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.1553-734X1553-735810.1371/journal.pcbi.1002844https://doaj.org/article/60fe7b6c3bd94dd8b27a6781459480462012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300424/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD) modulate substrate recognition at the Substrate Binding Domain (SBD). Herein, a comparative analysis of an allosteric (Hsp70-DnaK) and a non-allosteric structural homolog (Hsp110-Sse1) of the Hsp70 family is carried out through molecular dynamics simulations, starting from different conformations and ligand-states. Analysis of ligand-dependent modulation of internal fluctuations and local deformation patterns highlights the structural and dynamical changes occurring at residue level upon ATP-ADP exchange, which are connected to the conformational transition between closed and open structures. By identifying the dynamically responsive protein regions and specific cross-domain hydrogen-bonding patterns that differentiate Hsp70 from Hsp110 as a function of the nucleotide, we propose a molecular mechanism for the allosteric signal propagation of the ATP-encoded conformational signal.Federica ChiapporiIvan MerelliGiorgio ColomboLuciano MilanesiGiulia MorraPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 12, p e1002844 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Federica Chiappori Ivan Merelli Giorgio Colombo Luciano Milanesi Giulia Morra Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.
description	Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD) modulate substrate recognition at the Substrate Binding Domain (SBD). Herein, a comparative analysis of an allosteric (Hsp70-DnaK) and a non-allosteric structural homolog (Hsp110-Sse1) of the Hsp70 family is carried out through molecular dynamics simulations, starting from different conformations and ligand-states. Analysis of ligand-dependent modulation of internal fluctuations and local deformation patterns highlights the structural and dynamical changes occurring at residue level upon ATP-ADP exchange, which are connected to the conformational transition between closed and open structures. By identifying the dynamically responsive protein regions and specific cross-domain hydrogen-bonding patterns that differentiate Hsp70 from Hsp110 as a function of the nucleotide, we propose a molecular mechanism for the allosteric signal propagation of the ATP-encoded conformational signal.
format	article
author	Federica Chiappori Ivan Merelli Giorgio Colombo Luciano Milanesi Giulia Morra
author_facet	Federica Chiappori Ivan Merelli Giorgio Colombo Luciano Milanesi Giulia Morra
author_sort	Federica Chiappori
title	Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.
title_short	Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.
title_full	Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.
title_fullStr	Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.
title_full_unstemmed	Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.
title_sort	molecular mechanism of allosteric communication in hsp70 revealed by molecular dynamics simulations.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/60fe7b6c3bd94dd8b27a678145948046
work_keys_str_mv	AT federicachiappori molecularmechanismofallostericcommunicationinhsp70revealedbymoleculardynamicssimulations AT ivanmerelli molecularmechanismofallostericcommunicationinhsp70revealedbymoleculardynamicssimulations AT giorgiocolombo molecularmechanismofallostericcommunicationinhsp70revealedbymoleculardynamicssimulations AT lucianomilanesi molecularmechanismofallostericcommunicationinhsp70revealedbymoleculardynamicssimulations AT giuliamorra molecularmechanismofallostericcommunicationinhsp70revealedbymoleculardynamicssimulations
_version_	1718424728320868352

Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.

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