Homology- and coevolution-consistent structural models of bacterial copper-tolerance protein CopM support a ‘metal sponge’ function and suggest regions for metal-dependent protein-protein interactions

Copper is essential for life but toxic, therefore all organisms control tightly its intracellular abundance. Bacteria have indeed whole operons devoted to copper resistance, with genes that code for efflux pumps, oxidases, etc. Recently, the CopM protein of the CopMRS operon was described as a novel important element for copper tolerance in Synechocystis. This protein consists of a domain of unknown function, and was proposed to act as a periplasmic/extracellular copper binder. This work describes a bioinformatic study of CopM including structural models based on homology modeling and on residue coevolution, to help expand on its recent biochemical characterization. The protein is predicted to be periplasmic but membrane-anchored, not secreted. Two disordered regions are predicted, both possibly involved in protein-protein interactions. The 3D models disclose a 4-helix bundle with several potential copper-binding sites, most of them largely buried inside the bundle lumen. Some of the predicted copper-binding sites involve residues from the disordered regions, suggesting they could gain structure upon copper binding and thus possibly modulate the interactions they mediate. All models are provided as PDB files in the Supporting Information and can be visualized online at http://lucianoabriata.altervista.org/modelshome.html Note (January 2017): Recent X-ray structures of apo, copper- and silver-bound CopM are < 3Å RMSD away from the models, and reveal metal-dependent structural flexibility (Zhao et al Acta Crystallogr D Struct Biol. 2016)