Nine‐Heme Cytochrome c

Abstract

Nine heme cytochrome c (9Hcc) is a monomeric multi‐heme cytochrome c found in the sulfate‐reducing bacteria of Desulfovibrio desulfuricans (Dd) ATCC 27774 and Desulfovibrio desulfuricans Essex 6. The polypeptide chain comprises 296 residues and wraps around nine hemes of type‐c that bind the polypeptide chain through thioether bridges to cysteine residues. This represents the first known structure of a multi‐heme cytochrome where copies of a tetra‐heme cytochrome c 3 ‐like fold are present in the same polypeptide chain. The high homology between 9Hcc and the C‐terminal region of Desulfovibrio vulgaris Hildenborough (DvH) Hmc, as well as the presence of the 9Hcc gene within an operon similar to that of the DvH Hmc, strongly support the proposal that 9Hcc is the high‐molecular‐weight cytochrome of Dd. Several in vitro studies, as well as our crystallographic and modeling studies suggest that cytochrome c 3 is the mediator between the [NiFe] hydrogenase and 9Hcc in Dd.

A new paradigm of multiheme cytochrome evolution by grafting and pruning protein modules

“…The timeline for their emergence is typically thought to progress by fusion of redox modules towards more complex MHC. These can reach up to 16 hemes for structurally characterized MHC, but genes coding putative MHC containing as much as 113 hemes per polypeptide chain have been reported (Roldán et al 1998; Arménia Carrondo et al 2006; Santos-Silva et al 2007; Clarke et al 2011; Pokkuluri et al 2011; Pereira et al 2017; Edwards et al 2020; Leu et al 2020). Towards understanding the evolution of MHC we focused our attention on a group of MHC that is involved in the biogeochemical cycles of iron, nitrogen and sulfur.…”

“…MHC were abundantly employed by nature in the development of multiple biogeochemical cycles across large time scales, which were of high importance for the colonization of all extant ecological niches of life on earth. Previous proposals for the evolution of MHC have been biased towards gene fusion events (Roldán et al 1998; Arménia Carrondo et al 2006; Santos-Silva et al 2007; Clarke et al 2011; Pokkuluri et al 2011; Pereira et al 2017; Edwards et al 2020). Our study changes this perspective by showing that fission of heterogeneous redox modules also drives the evolution of MHC and should be a priori equally considered.…”

“…Nevertheless, the current paradigm for the emergence of the different known MHC follows the proposed fusion of redox modules, going from simple MHC to more complex and containing more heme cofactors per polypeptide chain. This comes from the observation of the presence of repetitive redox modules in MHC that has enabled to relate different MHC families (Roldán et al 1998; Arménia Carrondo et al 2006; Santos-Silva et al 2007; Clarke et al 2011; Pokkuluri et al 2011; Pereira et al 2017; Edwards et al 2020).…”