Studying Human Diseases via Magnetotactic Bacteria: Structure-Function Characterization of MamM Cytoplasmic Domain M250P - The Israel Society for Biochemistry & Molecular Biology (ISBMB) Abstract Submission Form

Shiran Barber-Zucker ^1,2 Dror Sherf ¹ Yotam Navon ^3,4 Geula Davidov ^1,2 Jordan H. Chill ⁵ Ronit Bitton ^3,4 Raz Zarivach ^1,2

¹Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva
²The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva
³Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva
⁴Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva
⁵Department of Chemistry, Bar-Ilan University, Ramat-Gan

The cation diffusion facilitator (CDF) protein family is a highly conserved, metal ion efflux transporter family that maintains divalent transition metal cation homeostasis. Human CDF proteins are named Zinc Transporters (ZnT) 1-10. Different mutations within ZnT proteins were shown to enhance or cause a variety of diseases, such as zinc deficiency and Parkinsonism. The missense mutation L349P in the manganese transporter ZnT-10 was shown to be related to manganese accumulation in cells, hepatomegaly and dystonia. We use the magnetosome-associated protein MamM cytosolic C-terminal domain (CTD) from the magnetotactic bacteria (MTB) strain Magnetospirillum gryphiswaldense MSR-1, a member of the CDF protein family, as a homologous model to study ZnT-10 L349P mutation. Magnetosomes are sub-cellular organelles in MTB that biomineralize ~30-120 nm single crystals of magnetite or greigite, and enable the MTB to orient themselves along geomagnetic fields. MamM is suspected to transport Fe(II) into the magnetosome by exploiting the proton motive force and participate in magnetite formation. In this work, we made a structural model for ZnT-10 CTD, found the L349 parallel amino acid in MamM CTD known structure and characterized the structural changes occurred by the homologous mutation, MamM CTD M250P. This work enables better understanding of the mutation-related disease mechanisms.