title: Cation diffusion facilitators transport initiation and regulation is mediated by cation induced conformational changes of the cytoplasmic domain.
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.
authors.affiliation: Department of Life Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel; National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Zeytuni
authors.affiliation: Ludwig Maximillian University of Munich, Department of Biology I, Martinsried, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Uebe
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Maes
authors.affiliation: Department of Life Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel; National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Geula
authors.initials: G
authors.lastname: Davidov
authors.affiliation: Department of Chemistry, Ben Gurion University of the Negev, Beer-Sheva, Israel; Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Baram
authors.affiliation: Ludwig Maximillian University of Munich, Department of Biology I, Martinsried, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Raschdorf
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Nadav-Tsubery
authors.affiliation: Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Sofiya
authors.initials: S
authors.lastname: Kolusheva
authors.affiliation: Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Beer-Sheva, Israel; Department of Chemical Engineering, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Bitton
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Goobes
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
authors.affiliation: Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Beer-Sheva, Israel; Department of Chemical Engineering, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Miller
authors.affiliation: Ludwig Maximillian University of Munich, Department of Biology I, Martinsried, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schüler
authors.affiliation: Department of Life Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel; National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism*; D006801:Humans; D055944:Magnetosomes / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D055503:Protein Multimerization; D014961:X-Ray Diffraction; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D002413:Cations, Divalent; D015032:Zinc