5.B.9 The Porin-Cytochrome c (Cyc2) Family 

Bacteria transport electrons across the cell envelope to external electron donors/acceptors. In Gram-negative bacteria, electron transfer across the outer membrane involves the use of an outer membrane β-barrel/cytochrome. These can be in the form of a porin-cytochrome protein, such as Cyc2 of the acidophilic bacterium, Acidithiobacillus ferrooxidans (White et al. 2016).  CycC has 570 aas, an N-terminal α-TMS (leader sequence), and 18 predicted transmembrane β-strands.

The iron respiratory chain of Acidithiobacillus ferrooxidans involves various metalloenzymes. Castelle et al. 2008 demonstrated that the oxygen reduction pathway from ferrous iron (the downhill pathway) is organized as a supercomplex constituted of proteins located in the outer and inner membranes as well as in the periplasm. The outer membrane-bound cytochrome c, Cyc2, was purified and proved to be responsible for iron oxidation; its redox potential was the highest measured to date for a cytochrome c. The organization of metalloproteins inside the supramolecular structure was specified by protein-protein interactions. The isolated complex spanning the two membranes had iron oxidase as well as oxygen reductase activities, indicating functional electron transfer between the first iron electron acceptor, Cyc2, and the Cu(A) center of cytochrome c oxidase aa₃. O₂ reduction from ferrous iron is coupled to the energy-consuming reduction of NAD⁺(P) from ferrous iron (uphill pathway) required for CO₂ fixation and other anabolic processes. Besides the proteins involved in O₂ reduction, there were additional proteins in the supercomplex involved in the uphill pathway (bc complex and cytochrome Cyc(42)), suggesting a possible physical link between these two pathways (Castelle et al. 2008; Liu et al. 2013; Kucera et al. 2016).

The generalized reaction catalyzed by Cyc2 is:

electron from Fe²⁺ (out) → Fe³⁺ (out) + electron (in a periplasmic protein)