title: Bacterial magnetosome biomineralization--a novel platform to study molecular mechanisms of human CDF-related Type-II diabetes.
abstract: Cation diffusion facilitators (CDF) are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all organisms. CDFs were found to be involved in numerous human health conditions, such as Type-II diabetes and neurodegenerative diseases. In this work, we established the magnetite biomineralizing alphaproteobacterium Magnetospirillum gryphiswaldense as an effective model system to study CDF-related Type-II diabetes. Here, we introduced two ZnT-8 Type-II diabetes-related mutations into the M. gryphiswaldense MamM protein, a magnetosome-associated CDF transporter essential for magnetite biomineralization within magnetosome vesicles. The mutations' effects on magnetite biomineralization and iron transport within magnetosome vesicles were tested in vivo. Additionally, by combining several in vitro and in silico methodologies we provide new mechanistic insights for ZnT-8 polymorphism at position 325, located at a crucial dimerization site important for CDF regulation and activation. Overall, by following differentiated, easily measurable, magnetism-related phenotypes we can utilize magnetotactic bacteria for future research of CDF-related human diseases.
authors.affiliation: Department of Life Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel; The 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, Dept. 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; The 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, Dept. Biology I, Martinsried, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Raschdorf
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: 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: Yifat
authors.initials: Y
authors.lastname: Miller
authors.affiliation: Ludwig Maximillian University of Munich, Dept. 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; The 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: D000483:Alleles; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D052203:Ferrosoferric Oxide / Q000378:metabolism; D006801:Humans; D055944:Magnetosomes / Q000378:metabolism*; D042201:Magnetospirillum / Q000166:cytology* / Q000378:metabolism*; D008903:Minerals / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015032:Zinc / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D008903:Minerals; D015032:Zinc; D052203:Ferrosoferric Oxide