title: Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance.
abstract: Cation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome-associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins' proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human.
authors.affiliation: Department of Life Sciences and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Shiran
authors.initials: S
authors.lastname: Barber-Zucker
authors.affiliation: Department of Microbiology, University of Bayreuth, Bayreuth, 95447, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Uebe
authors.affiliation: Department of Life Sciences and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Geula
authors.initials: G
authors.lastname: Davidov
authors.affiliation: Department of Chemical Engineering and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Navon
authors.affiliation: Department of Life Sciences and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Sherf
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Jordan H
authors.initials: JH
authors.lastname: Chill
authors.affiliation: Department of Life Sciences and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Kass
authors.affiliation: Department of Chemical Engineering and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Bitton
authors.affiliation: Department of Microbiology, University of Bayreuth, Bayreuth, 95447, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schüler
authors.affiliation: Department of Life Sciences and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, 8410501, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002942:Circular Dichroism; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D000072417:Protein Domains; D017510:Protein Folding; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein; D000075703:Zinc Transporter 8 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8