title: A systematic investigation of multiheme c-type cytochromes in prokaryotes.
abstract: Multiheme c-type cytochromes (MHCs) are metalloproteins that can play various biochemical roles, including enzymatic activity and electron transfer. As electron transfer proteins, the presence of multiple heme cofactors in the vicinity allows electrons to rapidly travel relatively long distances. MHCs are often characterized by relatively low structural complexity, with the heme cofactors being largely responsible for maintaining the structure in place, owing to the protein-heme covalent linkages. In this work, we analyzed an extensive ensemble of 594 complete prokaryotic proteomes, amounting to more than 1.9 million sequences, to characterize their content in MHCs. We identified 1,659 MHCs in 258 organisms. The presence of MHCs was found to correlate quite well with the capability of an organism to synthesize or take up heme. For two organisms, the presence of MHCs in the proteome could be taken as a hint to the presence of divergent heme uptake pathways. The most common numbers of heme-binding motifs in a sequence were four (25%) and two (23%), followed by five (13%) and ten (9.8%). The average protein-to-heme ratio was relatively similar for all MHCs, except diheme proteins, regardless of the number of motifs at around 60 +/- 30. The latter ratio could in favorable cases be a useful indicator for functional assignments of novel MHCs. Finally, we showed that the amount of structural information currently available for MHCs is limited with respect to the diversity of this broad class of metalloproteins. Experimental efforts in the structural investigation of MHCs are thus warranted.
authors.affiliation: Magnetic Resonance Center, University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Sharma
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cavallaro
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D003198:Computer Simulation; D003574:Cytochrome c Group / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006418:Heme; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry / Q000378:metabolism
chemical_list: D003574:Cytochrome c Group; D020543:Proteome; D006418:Heme