Understanding cation discrimination and transport regulation in magnetotactic bacteria

Divalent transition metal cations (DTMCs), such as Fe, Cu, and Mn, participate in many biological processes. They are co-factors in thousands of enzymes, involved in hormone secretion and neuronal activities under physiological and pathological conditions and are involved in photosynthetic processes. Understanding what controls the transport and its selectivity towards DTMCs is crucial for the study of metal homeostasis through the phylogenetic tree. In this work, we elucidated the structure-function relationships of MamM and MamB, which are involved in iron transport during magnetite biomineralization and constitute a prototypical member of the ubiquitous class of cation diffusion facilitators (CDFs). We used an interdisciplinary approach combining structural determination, biophysical characterizations, in vivo genetics and cellular imaging, to uncover the function(s) of MamM and MamB, and to elucidate the structural effects of mutations. This combined use of microbiological, biochemical, and microscopic techniques helped to determine the functional importance of key residues in CDFs, mapped onto the C-terminal domain. These residues are needed for MamM and MamB overall function in vivo. Furthermore, it allows us to provide the first mechanistic details for the CDF activation via its CTD. The results of our interdisciplinary and collaborative approach not only improved the understanding of magnetite biomineralization but also yielded broader insights into ion discrimination by CDF proteins and their regulation.