Computational Structure Prediction Provides a Plausible Mechanism for Electron Transfer by the Outer Membrane Protein Cyc2 fromAcidithiobacillus ferrooxidans

Abstract

Cyc2 is the key protein in the outer membrane of Acidithiobacillus ferrooxidans that mediates electron transfer between extracellular inorganic iron and the intracellular central metabolism. This cytochrome c is specific for iron and interacts with periplasmic proteins to complete a reversible electron transport chain. A structure of Cyc2 has not yet been characterized experimentally. Here we describe a structural model of Cyc2, and associated proteins, to highlight a plausible mechanism for the ferrous iron electron transfer chain. A comparative modeling protocol specific for trans membrane beta barrel (TMBB) proteins in acidophilic conditions (pH ~2) was applied to the primary sequence of Cyc2. The proposed structure has three main regimes: extracellular loops exposed to low-pH conditions, a TMBB, and a N-terminal cytochrome-like region within the periplasmic space. The Cyc2 model was further refined by identifying likely iron and heme docking sites. This represents the first computational model of Cyc2 that accounts for the membrane microenvironment and the acidity in the extracellular matrix. This approach can be used to model other TMBBs which can be critical for chemolithotrophic microbial growth.

Molecular Mechanisms of Microbial Extracellular Electron Transfer: The Importance of Multiheme Cytochromes

“…Recently, a cultured-based study associated with transcriptomics assays also demonstrated that the cytochrome Cyc2 participates in the Fe(II) oxidation process [106]. Cyc2 is predicted to be a transmembrane beta barrel protein with an N-terminal cytochrome-like region [107]. S. lithotrophicus ES-1 contains three cyc2 genes that are adjacent to one another in the genome, and that are more expressed than mtoA in Fe(II)-citrate cultures.…”