Bacterial magnetosome biomineralization--a novel platform to study molecular mechanisms of human CDF-related Type-II diabetes

Natalie Zeytuni; René Uebe; Michal Maes; Geula Davidov; Michal Baram; Oliver Raschdorf; Assaf Friedler; Yifat Miller; Dirk Schüler; Raz Zarivach

doi:10.1371/journal.pone.0097154

Bacterial magnetosome biomineralization--a novel platform to study molecular mechanisms of human CDF-related Type-II diabetes

PLoS One. 2014 May 12;9(5):e97154. doi: 10.1371/journal.pone.0097154. eCollection 2014.

Authors

Affiliations

¹ 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.
² Ludwig Maximillian University of Munich, Dept. Biology I, Martinsried, Germany.
³ Institute of Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
⁴ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Amino Acid Sequence
Bacterial Proteins / chemistry
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Cation Transport Proteins / chemistry
Cation Transport Proteins / genetics
Cation Transport Proteins / metabolism*
Diabetes Mellitus, Type 2 / genetics
Diabetes Mellitus, Type 2 / metabolism*
Ferrosoferric Oxide / metabolism
Humans
Magnetosomes / metabolism*
Magnetospirillum / cytology*
Magnetospirillum / metabolism*
Minerals / metabolism*
Models, Molecular
Molecular Sequence Data
Mutation
Protein Multimerization
Protein Stability
Protein Structure, Quaternary
Protein Structure, Tertiary
Zinc / metabolism

Substances

Bacterial Proteins
Cation Transport Proteins
Minerals
Zinc
Ferrosoferric Oxide

Grants and funding

This research was supported by grants from the GIF (German-Israeli Foundation for Scientific Research and Development), the European Cooperation in Science and Technology (COST action CM0902), the Israeli Ministry of Science and Technology, the Deutsche Forschungsgemeinschaft (grant SCHU 1080/13-1) and the FP7 of the European Union (collaborative grant NMP4-SL-2010-245542-Bio2MaN4MRI). AF is supported by a starting grant from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement n ° 203413 and by the Minerva Center for bio-hybrid complex systems. YM is supported by the FP7-PEOPLE-2011-CIG, research grant no. 303741. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.