The Crystal Structure of the Hexadeca-Heme Cytochrome Hmc and a Structural Model of Its Complex with Cytochrome c3

Abstract

Sulfate-reducing bacteria contain a variety of multi-heme c-type cytochromes. The cytochrome of highest molecular weight (Hmc) contains 16 heme groups and is part of a transmembrane complex involved in the sulfate respiration pathway. We present the 2.42 A resolution crystal structure of the Desulfovibrio vulgaris Hildenborough cytochrome Hmc and a structural model of the complex with its physiological electron transfer partner, cytochrome c(3), obtained by NMR restrained soft-docking calculations. The Hmc is composed of three domains, which exist independently in different sulfate-reducing species, namely cytochrome c(3), cytochrome c(7), and Hcc. The complex involves the last heme at the C-terminal region of the V-shaped Hmc and heme 4 of cytochrome c(3), and represents an example for specific cytochrome-cytochrome interaction.

Transient complexes of redox proteins: structural and dynamic details from NMR studies

“…According to the model proposed for Cc 3 -FeHase interaction, haem 4 of Cc 3 is the entrance gate of electrons to the cytochrome. These results, in conjunction with those obtained for the Cc 3 -CHmc complex (Czjzek et al, 2002), seem to exclude the possibility of ternary complex formation and, instead, favour the idea of Cc 3 acting as an electron shuttle between FeHase and CHmc (ElAntak et al, 2003).…”

“…CHmc is a periplasmic, high-molecular-weight cytochrome containing 16 haem groups. The X-ray structure of DvH CHmc (Czjzek et al, 2002; PDB entry 1gws) revealed a modular organization in three domains: the N-terminal domain I, homologous to the 3-haem-containing cytochrome c 7 ; domain II, similar to cytochromes of the c 3 type; and the C-terminal domain III, with a spatial arrangement similar to that of the 9-haem-containing cytochrome Hcc. (Czjzek et al, 2002).…”

“…Ten residues on Cc 3 were found to be affected by CHmc. These NMR results were used as constraints to filter the solutions obtained from ab initio BiGGER docking simulations and thereby generate a structural model of the interaction between the two proteins (Czjzek et al, 2002). According to this model, Cc 3 interacts with domain III of CHmc and electron transfer takes place between haem 4 of the former and haem 616 of the latter.…”

A Post-Genomic View of the Ecophysiology, Catabolism and Biotechnological Relevance of Sulphate-Reducing Prokaryotes

“…Other cytochromes of the TpIc 3 family are associated with transmembrane redox complexes described below (Matias et al, 2005;Pereira et al, 2007;. These include the 16-haem high molecular mass cytochrome (HmcA), a subunit of the Hmc complex (Czjzek et al, 2002;Matias et al, 2002), and the 9-haem cytochrome c (NhcA), a subunit of the Nhc complex (Matias et al, 1999), both of which contain several TpIc 3 domains. Another member of the family is the tetrahaem Type II cytochrome c 3 (TpIIc 3 or TmcA), which has small structural differences relative to TpIc 3 , but lacks its characteristic positive surface region around haem IV, the site of interaction with hydrogenases/formate dehydrogenases, and has a negative region around haem I (Norager, Legrand, Pieulle, Hatchikian, & Roth, 1999;Valente et al, 2001).…”

Crystal Structure of the 16 Heme Cytochrome from Desulfovibrio gigas: A Glycosylated Protein in a Sulphate-reducing Bacterium

“…11 Until now, HmcA, a 16 heme cytochrome, is the only protein from this group that has been characterized structurally. 12,13 HmcA has been isolated from the periplasm of Dg and Desulfovibrio vulgaris Hildenborough (Dv) organisms. Even though it contains a signal sequence for periplasmic export, 14 it can be found, to large extent, in the membrane fraction.…”