Structural model of Cyc2, the primary electron acceptor of Acidithiobacillus ferrooxidans’ respiratory chain, as a modular cytochrome - β-barrel fusion protein, and mechanistic proposals based on this model

Abstract

Abstract. Acidithiobacillus ferrooxidans oxidizes Fe(II) to Fe(III) to feed electrons into its respiratory chain. The primary electron acceptor of this complex system is Cyc2, an outer membrane protein of unknown structure. This work proposes a feasible model of Cyc2's global structure, based on homology modeling, residue-residue coevolution data, bioinformatics predictions and limited knowledge about Cyc2's function. The proposal is that the sequence segment spanning residues ~30 to ~90 folds as a cytochrome-like domain that contains a heme group which would presumably bind and oxidize external Fe(II), whereas the remaining segment from residue ~90 until the end adopts a β-barrel fold similar to that of most outer membrane proteins. Such model differs strongly from a published model, but is backed up by more data and is more compatible with the known topology of outer membrane proteins and with Cyc2's function of internalizing reducing equivalents. The small size of the cytochrome-like domain would allow it to reside inside, and/or slide through, the β-barrel domain, thus communicating in a controlled fashion the extracellular medium with the periplasm to import electrons through the outer membrane. All the models discussed are provided as PyMOL session files in the Supporting Information and can be visualized online at