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Zeytuni, Natalie; Uebe, Rene; Maes, Michal; Davidov, Geula; Baram, Michal; Raschdorf, Oliver; Nadav-Tsubery, Merav; Kolusheva, Sofiya; Bitton, Ronit; Goobes, Gil; Friedler, Assaf; Miller, Yifat; Schueler, Dirk; Zarivach, Raz (2014): Cation Diffusion Facilitators Transport Initiation and Regulation Is Mediated by Cation Induced Conformational Changes of the Cytoplasmic Domain.
In: PLOS ONE 9(3), e92141
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Abstract

Cation diffusion facilitators (CDF) are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all domains of life. CDF's were shown to be involved in several human diseases, such as Type-II diabetes and neurodegenerative diseases. In this work, we employed a multi-disciplinary approach to study the activation mechanism of the CDF protein family. For this we used MamM, one of the main ion transporters of magnetosomes - bacterial organelles that enable magnetotactic bacteria to orientate along geomagnetic fields. Our results reveal that the cytosolic domain of MamM forms a stable dimer that undergoes distinct conformational changes upon divalent cation binding. MamM conformational change is associated with three metal binding sites that were identified and characterized. Altogether, our results provide a novel auto-regulation mode of action model in which the cytosolic domain's conformational changes upon ligand binding allows the priming of the CDF into its transport mode.