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The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis

Maintaining iron homeostasis is fundamental for almost all living beings, and its deregulation correlates with severe and debilitating pathologies. The process is made more complicated by the omnipresence of iron and by its role as a fundamental component of a number of crucial metallo proteins. The...

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Autores principales: Hognon, Cécilia, Bignon, Emmanuelle, Harle, Guillaume, Touche, Nadège, Grandemange, Stéphanie, Monari, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469783/
https://www.ncbi.nlm.nih.gov/pubmed/34572542
http://dx.doi.org/10.3390/biom11091329
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author Hognon, Cécilia
Bignon, Emmanuelle
Harle, Guillaume
Touche, Nadège
Grandemange, Stéphanie
Monari, Antonio
author_facet Hognon, Cécilia
Bignon, Emmanuelle
Harle, Guillaume
Touche, Nadège
Grandemange, Stéphanie
Monari, Antonio
author_sort Hognon, Cécilia
collection PubMed
description Maintaining iron homeostasis is fundamental for almost all living beings, and its deregulation correlates with severe and debilitating pathologies. The process is made more complicated by the omnipresence of iron and by its role as a fundamental component of a number of crucial metallo proteins. The response to modifications in the amount of the free-iron pool is performed via the inhibition of ferritin translation by sequestering consensus messenger RNA (mRNA) sequences. In turn, this is regulated by the iron-sensitive conformational equilibrium between cytosolic aconitase and IRP1, mediated by the presence of an iron–sulfur cluster. In this contribution, we analyze by full-atom molecular dynamics simulation, the factors leading to both the interaction with mRNA and the conformational transition. Furthermore, the role of the iron–sulfur cluster in driving the conformational transition is assessed by obtaining the related free energy profile via enhanced sampling molecular dynamics simulations.
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spelling pubmed-84697832021-09-27 The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis Hognon, Cécilia Bignon, Emmanuelle Harle, Guillaume Touche, Nadège Grandemange, Stéphanie Monari, Antonio Biomolecules Article Maintaining iron homeostasis is fundamental for almost all living beings, and its deregulation correlates with severe and debilitating pathologies. The process is made more complicated by the omnipresence of iron and by its role as a fundamental component of a number of crucial metallo proteins. The response to modifications in the amount of the free-iron pool is performed via the inhibition of ferritin translation by sequestering consensus messenger RNA (mRNA) sequences. In turn, this is regulated by the iron-sensitive conformational equilibrium between cytosolic aconitase and IRP1, mediated by the presence of an iron–sulfur cluster. In this contribution, we analyze by full-atom molecular dynamics simulation, the factors leading to both the interaction with mRNA and the conformational transition. Furthermore, the role of the iron–sulfur cluster in driving the conformational transition is assessed by obtaining the related free energy profile via enhanced sampling molecular dynamics simulations. MDPI 2021-09-09 /pmc/articles/PMC8469783/ /pubmed/34572542 http://dx.doi.org/10.3390/biom11091329 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hognon, Cécilia
Bignon, Emmanuelle
Harle, Guillaume
Touche, Nadège
Grandemange, Stéphanie
Monari, Antonio
The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis
title The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis
title_full The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis
title_fullStr The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis
title_full_unstemmed The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis
title_short The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis
title_sort iron maiden. cytosolic aconitase/irp1 conformational transition in the regulation of ferritin translation and iron hemostasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469783/
https://www.ncbi.nlm.nih.gov/pubmed/34572542
http://dx.doi.org/10.3390/biom11091329
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