Investigation of the Molecular Mechanisms of the Eukaryotic Cytochrome- Maturation System

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2022 Apr 23

PMID 35454139

Authors

Ana V Silva

Maria O Firmino

Nazua L Costa

Ricardo O Louro

Catarina M Paquete

Affiliations

Soon will be listed here.

Abstract

Cytochromes- are ubiquitous heme proteins with enormous impact at the cellular level, being key players in metabolic processes such as electron transfer chains and apoptosis. The assembly of these proteins requires maturation systems that catalyse the formation of the covalent thioether bond between two cysteine residues and the vinyl groups of the heme. System III is the maturation system present in Eukaryotes, designated CcHL or HCCS. This System requires a specific amino acid sequence in the apocytochrome to be recognized as a substrate and for heme insertion. To explore the recognition mechanisms of CcHL, the bacterial tetraheme cytochrome STC from MR-1, which is not a native substrate for System III, was mutated to be identified as a substrate. The results obtained show that it is possible to convert a bacterial cytochrome as a substrate by CcHL, but the presence of the recognition sequence is not the only factor that induces the maturation of a holocytochrome by System III. The location of this sequence in the polypeptide also plays a role in the maturation of the -type cytochrome. Furthermore, CcHL appears to be able to catalyse the binding of only one heme per polypeptide chain, being unable to assemble multiheme cytochromes , in contrast with bacterial maturation systems.

Citing Articles

Genetically Encoded Fluorescent Probe for Detection of Heme-Induced Conformational Changes in Cytochrome c.

Genceroglu M, Cavdar C, Manioglu S, Bayraktar H Biosensors (Basel). 2023; 13(9).

PMID: 37754124 PMC: 10526477. DOI: 10.3390/bios13090890.

References

Fonseca B, Saraiva I, Paquete C, Soares C, Pacheco I, Salgueiro C . The tetraheme cytochrome from Shewanella oneidensis MR-1 shows thermodynamic bias for functional specificity of the hemes. J Biol Inorg Chem. 2008; 14(3):375-85. DOI: 10.1007/s00775-008-0455-7. View

Korb H, Neupert W . Biogenesis of cytochrome c in Neurospora crassa. Synthesis of apocytochrome c, transfer to mitochondria and conversion to Holocytochrome c. Eur J Biochem. 1978; 91(2):609-20. DOI: 10.1111/j.1432-1033.1978.tb12714.x. View

Kranz R, Richard-Fogal C, Taylor J, Frawley E . Cytochrome c biogenesis: mechanisms for covalent modifications and trafficking of heme and for heme-iron redox control. Microbiol Mol Biol Rev. 2009; 73(3):510-28, Table of Contents. PMC: 2738134. DOI: 10.1128/MMBR.00001-09. View

Wimplinger I, Morleo M, Rosenberger G, Iaconis D, Orth U, Meinecke P . Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome. Am J Hum Genet. 2006; 79(5):878-89. PMC: 1698567. DOI: 10.1086/508474. View

Dumont M, Ernst J, Hampsey D, Sherman F . Identification and sequence of the gene encoding cytochrome c heme lyase in the yeast Saccharomyces cerevisiae. EMBO J. 1987; 6(1):235-41. PMC: 553382. DOI: 10.1002/j.1460-2075.1987.tb04744.x. View

Patel C, Lind M, Pielak G . Characterization of horse cytochrome c expressed in Escherichia coli. Protein Expr Purif. 2001; 22(2):220-4. DOI: 10.1006/prep.2001.1438. View

Babbitt S, Hsu J, Mendez D, Kranz R . Biosynthesis of Single Thioether c-Type Cytochromes Provides Insight into Mechanisms Intrinsic to Holocytochrome c Synthase (HCCS). Biochemistry. 2017; 56(26):3337-3346. PMC: 5551481. DOI: 10.1021/acs.biochem.7b00286. View

de Vitry C . Cytochrome c maturation system on the negative side of bioenergetic membranes: CCB or System IV. FEBS J. 2011; 278(22):4189-97. DOI: 10.1111/j.1742-4658.2011.08373.x. View

Arslan E, Schulz H, Zufferey R, Kunzler P, Thony-Meyer L . Overproduction of the Bradyrhizobium japonicum c-type cytochrome subunits of the cbb3 oxidase in Escherichia coli. Biochem Biophys Res Commun. 1998; 251(3):744-7. DOI: 10.1006/bbrc.1998.9549. View

10.

San Francisco B, Bretsnyder E, Kranz R . Human mitochondrial holocytochrome c synthase's heme binding, maturation determinants, and complex formation with cytochrome c. Proc Natl Acad Sci U S A. 2012; 110(9):E788-97. PMC: 3587199. DOI: 10.1073/pnas.1213897109. View

11.

Ferguson S . New perspectives on assembling c-type cytochromes, particularly from sulphate reducing bacteria and mitochondria. Biochim Biophys Acta. 2012; 1817(10):1754-8. DOI: 10.1016/j.bbabio.2012.05.004. View

12.

Olteanu A, Patel C, Dedmon M, Kennedy S, Linhoff M, Minder C . Stability and apoptotic activity of recombinant human cytochrome c. Biochem Biophys Res Commun. 2003; 312(3):733-40. DOI: 10.1016/j.bbrc.2003.10.182. View

13.

Pollock W, Rosell F, Twitchett M, Dumont M, Mauk A . Bacterial expression of a mitochondrial cytochrome c. Trimethylation of lys72 in yeast iso-1-cytochrome c and the alkaline conformational transition. Biochemistry. 1998; 37(17):6124-31. DOI: 10.1021/bi972188d. View

14.

Ow Y, Green D, Hao Z, Mak T . Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008; 9(7):532-42. DOI: 10.1038/nrm2434. View

15.

Morar A, Kakouras D, Young G, Boyd J, Pielak G . Expression of 15N-labeled eukaryotic cytochrome c in Escherichia coli. J Biol Inorg Chem. 1999; 4(2):220-2. DOI: 10.1007/s007750050307. View

16.

DICKERSON R . Cytochrome c and the evolution of energy metabolism. Sci Am. 1980; 242(3):137-53. View

17.

Slavotinek A . Genetics of anophthalmia and microphthalmia. Part 2: Syndromes associated with anophthalmia-microphthalmia. Hum Genet. 2018; 138(8-9):831-846. DOI: 10.1007/s00439-018-1949-1. View

18.

Mendez D, Lowder E, Tillman D, Sutherland M, Collier A, Rau M . Cryo-EM of CcsBA reveals the basis for cytochrome c biogenesis and heme transport. Nat Chem Biol. 2021; 18(1):101-108. PMC: 8712405. DOI: 10.1038/s41589-021-00935-y. View

19.

Verissimo A, Sanders J, Daldal F, Sanders C . Engineering a prokaryotic apocytochrome c as an efficient substrate for Saccharomyces cerevisiae cytochrome c heme lyase. Biochem Biophys Res Commun. 2012; 424(1):130-5. PMC: 4420188. DOI: 10.1016/j.bbrc.2012.06.088. View

20.

Sutherland M, Tran N, Tillman D, Jarodsky J, Yuan J, Kranz R . Structure-Function Analysis of the Bifunctional CcsBA Heme Exporter and Cytochrome Synthetase. mBio. 2018; 9(6). PMC: 6299221. DOI: 10.1128/mBio.02134-18. View