C-type cytochromes: diverse structures and biogenesis systems pose evolutionary problems

Abstract

C-type cytochromes are a structurally diverse group of haemoproteins, which are related by the occurrence of haem covalently attached to a polypeptide via two thioether bonds formed by the vinyl groups of haem and cysteine side chains in a CXXCH peptide motif. Remarkably, three different post-translational systems for forming these cytochromes have been identified. The evolution of both the proteins themselves and the biogenesis systems poses many questions to which answers are currently being sought. In this article we review the progress that has been made in understanding the need for covalent attachment of haem to proteins in cytochromes c and the complex systems involved in their formation.

c-Type Cytochrome Assembly in Saccharomyces cerevisiae: A Key Residue for Apocytochrome c1/Lyase Interaction

“…This disulfide needs to be reduced to a dithiol to provide free sulfhydryls for the heme ligation. Consistent with this view is the fact that groups of specific oxido-reductases that constitute a transmembrane dithiol-disulfide relay from the cytosol to the periplasmic space have been shown to function as c-type cytochrome assembly factors (Allen et al 2003;Kadokura et al 2003;Mapller and Hederstedt 2006;Sanders et al 2010). The proposal that the components of this pathway control the in vivo redox status of the CXXCH sulfhydryls has been inferred from the presence of motifs in their protein sequences that are consistent with a function in redox chemistry and also from the demonstration that their recombinant forms participate in dithiol-disulfide exchange reactions (Monika et al 1997;Setterdahl et al 2000).…”

c-Type Cytochrome Assembly in Saccharomyces cerevisiae: A Key Residue for Apocytochrome c1/Lyase Interaction

“…This disulfide needs to be reduced to a dithiol to provide free sulfhydryls for the heme ligation. Consistent with this view is the fact that groups of specific oxido-reductases that constitute a transmembrane dithiol-disulfide relay from the cytosol to the periplasmic space have been shown to function as c-type cytochrome assembly factors (Allen et al 2003;Kadokura et al 2003;Mapller and Hederstedt 2006;Sanders et al 2010). The proposal that the components of this pathway control the in vivo redox status of the CXXCH sulfhydryls has been inferred from the presence of motifs in their protein sequences that are consistent with a function in redox chemistry and also from the demonstration that their recombinant forms participate in dithiol-disulfide exchange reactions (Monika et al 1997;Setterdahl et al 2000).…”

Radical Mediated Rapid In Vitro Formation of c-Type Cytochrome

“…However, pathway B would be more favorable as it passes through a much more stable secondary radical intermediate adjacent to the porphyrin ring. This is contrary to the in vivo formation of Cyt c , which has a thioether bond produced through the thermodynamically unfavorable pathway A in the current reaction scheme [4,5,32,33,34]. This highlights the unusual selectivity of the enzymatic thioether formation in Cyt c , which is believed to require 10 accessory proteins (namely Cyt c maturation proteins) [4,5,34].…”

GHP, a new c‐type green heme protein from Halochromatium salexigens and other proteobacteria

“…Peptides covering the sequence regions 32-44 (1457.7 Da) and 32-48 (1941.9 Da) were shown to contain a modified cysteine, by a mass shift of 57 Da to 1514.7 Da and 1998.9 Da, respectively (data not shown). As expected from the conventional CXXCH heme-binding motif, the two other cysteines are involved in covalent heme binding [9].…”

c-Type Cytochrome Assembly in Saccharomyces cerevisiae: A Key Residue for Apocytochrome c1/Lyase Interaction

“…This disulfide needs to be reduced to a dithiol to provide free sulfhydryls for the heme ligation. Consistent with this view is the fact that groups of specific oxido-reductases that constitute a transmembrane dithiol-disulfide relay from the cytosol to the periplasmic space have been shown to function as c-type cytochrome assembly factors (Allen et al 2003;Kadokura et al 2003;Mapller and Hederstedt 2006;Sanders et al 2010). The proposal that the components of this pathway control the in vivo redox status of the CXXCH sulfhydryls has been inferred from the presence of motifs in their protein sequences that are consistent with a function in redox chemistry and also from the demonstration that their recombinant forms participate in dithiol-disulfide exchange reactions (Monika et al 1997;Setterdahl et al 2000).…”

Radical Mediated Rapid In Vitro Formation of c-Type Cytochrome

“…However, pathway B would be more favorable as it passes through a much more stable secondary radical intermediate adjacent to the porphyrin ring. This is contrary to the in vivo formation of Cyt c , which has a thioether bond produced through the thermodynamically unfavorable pathway A in the current reaction scheme [4,5,32,33,34]. This highlights the unusual selectivity of the enzymatic thioether formation in Cyt c , which is believed to require 10 accessory proteins (namely Cyt c maturation proteins) [4,5,34].…”

GHP, a new c‐type green heme protein from Halochromatium salexigens and other proteobacteria

“…Peptides covering the sequence regions 32-44 (1457.7 Da) and 32-48 (1941.9 Da) were shown to contain a modified cysteine, by a mass shift of 57 Da to 1514.7 Da and 1998.9 Da, respectively (data not shown). As expected from the conventional CXXCH heme-binding motif, the two other cysteines are involved in covalent heme binding [9].…”

c-Type Cytochrome Assembly in Saccharomyces cerevisiae: A Key Residue for Apocytochrome c1/Lyase Interaction

“…This disulfide needs to be reduced to a dithiol to provide free sulfhydryls for the heme ligation. Consistent with this view is the fact that groups of specific oxido-reductases that constitute a transmembrane dithiol-disulfide relay from the cytosol to the periplasmic space have been shown to function as c-type cytochrome assembly factors (Allen et al 2003;Kadokura et al 2003;Mapller and Hederstedt 2006;Sanders et al 2010). The proposal that the components of this pathway control the in vivo redox status of the CXXCH sulfhydryls has been inferred from the presence of motifs in their protein sequences that are consistent with a function in redox chemistry and also from the demonstration that their recombinant forms participate in dithiol-disulfide exchange reactions (Monika et al 1997;Setterdahl et al 2000).…”

Radical Mediated Rapid In Vitro Formation of c-Type Cytochrome

“…However, pathway B would be more favorable as it passes through a much more stable secondary radical intermediate adjacent to the porphyrin ring. This is contrary to the in vivo formation of Cyt c , which has a thioether bond produced through the thermodynamically unfavorable pathway A in the current reaction scheme [4,5,32,33,34]. This highlights the unusual selectivity of the enzymatic thioether formation in Cyt c , which is believed to require 10 accessory proteins (namely Cyt c maturation proteins) [4,5,34].…”

GHP, a new c‐type green heme protein from Halochromatium salexigens and other proteobacteria

“…Peptides covering the sequence regions 32-44 (1457.7 Da) and 32-48 (1941.9 Da) were shown to contain a modified cysteine, by a mass shift of 57 Da to 1514.7 Da and 1998.9 Da, respectively (data not shown). As expected from the conventional CXXCH heme-binding motif, the two other cysteines are involved in covalent heme binding [9].…”