The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis.
Fiche publication
Date publication
septembre 2021
Journal
Biomolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GRANDEMANGE Stéphanie
Tous les auteurs :
Hognon C, Bignon E, Harle G, Touche N, Grandemange S, Monari A
Lien Pubmed
Résumé
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.
Mots clés
IRP, aconitase, free energy profiles, iron homeostasis, messenger RNA, molecular dynamics
Référence
Biomolecules. 2021 Sep 9;11(9):