Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches

Abstract RalF is an Arf GEF from Legionella pneumophilia, the bacterium that causes severe pneumonia. In its crystal structure, RalF is in the autoinhibited form. A large-scale domain motion is expected to lift the autoinhibition, the mechanism of which is still unknown. Since RalF is activated in t...

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Autores principales:	Balint Dudas, David Perahia, Erika Balog
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/959fe3fd1e35472f80ac15409616d5d0
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spelling	oai:doaj.org-article:959fe3fd1e35472f80ac15409616d5d02021-12-02T15:55:04ZRevealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches10.1038/s41598-021-89169-52045-2322https://doaj.org/article/959fe3fd1e35472f80ac15409616d5d02021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89169-5https://doaj.org/toc/2045-2322Abstract RalF is an Arf GEF from Legionella pneumophilia, the bacterium that causes severe pneumonia. In its crystal structure, RalF is in the autoinhibited form. A large-scale domain motion is expected to lift the autoinhibition, the mechanism of which is still unknown. Since RalF is activated in the presence of the membrane, its active structure and the structure of the RalF-Arf1 complex could not have been determined experimentally. On the simulation side, it has been proven that classical Molecular Dynamics (MD) alone is not efficient enough to map motions of such amplitude and determine the active conformation of RalF. In this article, using Molecular Dynamics with excited Normal Modes (MDeNM) combined with previous experimental findings we were able to determine the active RalF structure and the structure of the RalF-Arf1 complex in the presence of the membrane, bridging the gap between experiments and simulation.Balint DudasDavid PerahiaErika BalogNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Balint Dudas David Perahia Erika Balog Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
description	Abstract RalF is an Arf GEF from Legionella pneumophilia, the bacterium that causes severe pneumonia. In its crystal structure, RalF is in the autoinhibited form. A large-scale domain motion is expected to lift the autoinhibition, the mechanism of which is still unknown. Since RalF is activated in the presence of the membrane, its active structure and the structure of the RalF-Arf1 complex could not have been determined experimentally. On the simulation side, it has been proven that classical Molecular Dynamics (MD) alone is not efficient enough to map motions of such amplitude and determine the active conformation of RalF. In this article, using Molecular Dynamics with excited Normal Modes (MDeNM) combined with previous experimental findings we were able to determine the active RalF structure and the structure of the RalF-Arf1 complex in the presence of the membrane, bridging the gap between experiments and simulation.
format	article
author	Balint Dudas David Perahia Erika Balog
author_facet	Balint Dudas David Perahia Erika Balog
author_sort	Balint Dudas
title	Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
title_short	Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
title_full	Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
title_fullStr	Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
title_full_unstemmed	Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches
title_sort	revealing the activation mechanism of autoinhibited ralf by integrated simulation and experimental approaches
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/959fe3fd1e35472f80ac15409616d5d0
work_keys_str_mv	AT balintdudas revealingtheactivationmechanismofautoinhibitedralfbyintegratedsimulationandexperimentalapproaches AT davidperahia revealingtheactivationmechanismofautoinhibitedralfbyintegratedsimulationandexperimentalapproaches AT erikabalog revealingtheactivationmechanismofautoinhibitedralfbyintegratedsimulationandexperimentalapproaches
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Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches

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