Extracytoplasmic prosthetic group ligation to apoproteins: maturation of <i>c</i>‐type cytochromes

Turkarslan, Serdar; Sanders, Carsten; Daldal, Fevzi

doi:10.1111/j.1365-2958.2006.05148.x

Cited by 22 publications

(25 citation statements)

References 18 publications

(18 reference statements)

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“…Two thioether linkages and the fifth axial His are the basic features of c-type cytochromes (18,36). The essential role of the latter in formation of the former has been revealed for a genuine c-type and multiheme cytochrome gene in this work.…”

Section: Discussionmentioning

confidence: 78%

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Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c₃

et al. 2008

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Akutsu, H. (2008). Strategic roles of axial histidines in structure formation and redox regulation of tetraheme cytochrome c3. Biochemistry, 47 (36), 9405-9415. Strategic roles of axial histidines in structure formation and redox regulation of tetraheme cytochrome c3 AbstractTetraheme cytochrome c3 (cyt c3) exhibits extremely low reduction potentials and unique properties. Since axial ligands should be the most important factors for this protein, every axial histidine of Desulfovibrio vulgaris Miyazaki F cyt c3 was replaced with methionine, one by one. On mutation at the fifth ligand, the relevant heme could not be linked to the polypeptide, revealing the essential role of the fifth histidine in heme linking. The fifth histidine is the key residue in the structure formation and redox regulation of a c-type cytochrome. A crystal structure has been obtained for only H25M cyt c3. The overall structure was not affected by the mutation except for the sixth methionine coordination at heme 3. NMR spectra revealed that each mutated methionine is coordinated to the sixth site of the relevant heme in the reduced state, while ligand conversion takes place at hemes 1 and 4 during oxidation at pH 7. The replacement of the sixth ligand with methionine caused an increase in the reduction potential of the mutated heme of 222-244 mV. The midpoint potential of a triheme H52M cyt c3 is higher than that of the wild type by ∼50 mV, suggesting a contribution of the tetraheme architecture to the lowering of the reduction potentials. The hydrogen bonding of Thr24 with an axial ligand induces a decrease in reduction potential of ∼50 mV. In conclusion, the bishistidine coordination is strategically essential for the structure formation and the extremely low reduction potential of cyt c 3. © 2008 American Chemical Society. Koto, Kamigori, Hyogo 678-1297, Japan, The RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5248, Japan, and Faculty of Engineering, Yokohama National UniVersity, Hodogaya-ku, Yokohama 240-8501, Japan ReceiVed April 2, 2008; ReVised Manuscript ReceiVed July 18, 2008 ABSTRACT: Tetraheme cytochrome c 3 (cyt c 3 ) exhibits extremely low reduction potentials and unique properties. Since axial ligands should be the most important factors for this protein, every axial histidine of DesulfoVibrio Vulgaris Miyazaki F cyt c 3 was replaced with methionine, one by one. On mutation at the fifth ligand, the relevant heme could not be linked to the polypeptide, revealing the essential role of the fifth histidine in heme linking. The fifth histidine is the key residue in the structure formation and redox regulation of a c-type cytochrome. A crystal structure has been obtained for only H25M cyt c 3 . The overall structure was not affected by the mutation except for the sixth methionine coordination at heme 3. NMR spectra revealed that each mutated methionine is coordinated to the sixth site of the relevant heme in the reduced state, while ligand conversion takes place at hemes 1 and 4 during oxidation at pH ...

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Section: Discussionmentioning

confidence: 78%

“…We can conclude that the fifth axial His is essential not only for the redox regulation but also for the heme linking to c-type apocytochromes in S. oneidensis as well as in E. coli (31). There are three distinct types of Ccms, namely, types I, II, and III (36). The Ccms of S. oneidensis and E. coli are classified as type I.…”

Section: Discussionmentioning

confidence: 99%

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c₃

et al. 2008

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“…The cysteine residues of the CXXCH motif must be reduced to form the thioether bonds to the alpha carbons of the heme vinyl groups. Some recent reviews on cytochrome c synthesis have included thorough discussions of the thiol reduction components (58,157), and so the present review will only briefly describe these components. One aspect that makes cytochrome c synthesis even more phenomenal is that the polypeptide folds around the heme only after ligation, unlike the case for hemoglobins and other cytochromes, where protein folding occurs prior to heme binding.…”

Section: Heme Types and Modificationsmentioning

confidence: 99%

“…Figure 2 diagrams the thiol proteins (in red) which transfer reducing equivalents from inside the cell to outside. Since some aspects of assembly have been reviewed in the last 5 years (5,9,12,58,70,157), here we focus on selected emerging concepts. Because all proteins in systems I and II are integral membrane proteins, descriptions will be presented in the context of the two-dimensional topologies of the integral membrane proteins in the pathways.…”

Section: Cytochrome C Biogenesis: Three Systems and Some Emerging Spmentioning

confidence: 99%

CytochromecBiogenesis: Mechanisms for Covalent Modifications and Trafficking of Heme and for Heme-Iron Redox Control

Kranz¹,

Richard-Fogal²,

Taylor

et al. 2009

Microbiol Mol Biol Rev

230

372

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SUMMARY Heme is the prosthetic group for cytochromes, which are directly involved in oxidation/reduction reactions inside and outside the cell. Many cytochromes contain heme with covalent additions at one or both vinyl groups. These include farnesylation at one vinyl in hemes o and a and thioether linkages to each vinyl in cytochrome c (at CXXCH of the protein). Here we review the mechanisms for these covalent attachments, with emphasis on the three unique cytochrome c assembly pathways called systems I, II, and III. All proteins in system I (called Ccm proteins) and system II (Ccs proteins) are integral membrane proteins. Recent biochemical analyses suggest mechanisms for heme channeling to the outside, heme-iron redox control, and attachment to the CXXCH. For system II, the CcsB and CcsA proteins form a cytochrome c synthetase complex which specifically channels heme to an external heme binding domain; in this conserved tryptophan-rich “WWD domain” (in CcsA), the heme is maintained in the reduced state by two external histidines and then ligated to the CXXCH motif. In system I, a two-step process is described. Step 1 is the CcmABCD-mediated synthesis and release of oxidized holoCcmE (heme in the Fe+3 state). We describe how external histidines in CcmC are involved in heme attachment to CcmE, and the chemical mechanism to form oxidized holoCcmE is discussed. Step 2 includes the CcmFH-mediated reduction (to Fe+2) of holoCcmE and ligation of the heme to CXXCH. The evolutionary and ecological advantages for each system are discussed with respect to iron limitation and oxidizing environments.

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“…Because all cytochromes c function and are synthesized in the prokaryotic periplasm, mitochondrial intermembrane space, or chloroplast lumen, heme must be delivered to these sites, yet the molecular mechanisms of delivery are unknown. Cytochrome c synthesis is carried out by one of three pathways (systems I, II, and III) (6)(7)(8)(9)(10) and requires the formation of two thioether bonds between the cysteines of a CXXCH motif in the apoprotein and the vinyl groups of heme. For this covalent ligation to occur, the heme must be reduced (Fe 2ϩ ) (11,12), but the mechanism of heme reduction in vivo is unknown.…”

mentioning

confidence: 99%

CcsBA is a cytochrome c synthetase that also functions in heme transport

Frawley

Kranz

2009

Proc. Natl. Acad. Sci. U.S.A.

151

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Little is known about trafficking of heme from its sites of synthesis to sites of heme-protein assembly. We describe an integral membrane protein that allows trapping of endogenous heme to elucidate trafficking mechanisms. We show that CcsBA, a representative of a superfamily of integral membrane proteins involved in cytochrome c biosynthesis, exports and protects heme from oxidation. CcsBA has 10 transmembrane domains (TMDs) and reconstitutes cytochrome c synthesis in the Escherichia coli periplasm; thus, CcsBA is a cytochrome c synthetase. Purified CcsBA contains heme in an ''external heme binding domain'' for which two external histidines are shown to serve as axial ligands that protect the heme iron from oxidation. This is likely the active site of the synthetase. Furthermore, two conserved histidines in TMDs are required for heme to travel to the external heme binding domain. Remarkably, the function of CcsBA with mutations in these TMD histidines is corrected by exogenous imidazole, a result analogous to correction of heme binding by myoglobin when its proximal histidine is mutated. These data suggest that CcsBA has a heme binding site within the bilayer and that CcsBA is a heme channel.channel ͉ cofactor ͉ imidazole complementation ͉ biogenesis ͉ assembly

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Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c‐type cytochromes

Cited by 22 publications

References 18 publications

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c₃

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c₃

CytochromecBiogenesis: Mechanisms for Covalent Modifications and Trafficking of Heme and for Heme-Iron Redox Control

CcsBA is a cytochrome c synthetase that also functions in heme transport

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Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c‐type cytochromes

Cited by 22 publications

References 18 publications

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c3

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c3

CytochromecBiogenesis: Mechanisms for Covalent Modifications and Trafficking of Heme and for Heme-Iron Redox Control

CcsBA is a cytochrome c synthetase that also functions in heme transport

Contact Info

Product

Resources

About

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c₃

Strategic Roles of Axial Histidines in Structure Formation and Redox Regulation of Tetraheme Cytochrome c₃