Robert Kranz

Robert Kranz

Professor Emeritus of Biology
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Cytochrome c assembly (Overview)

Since 1987 our group has studied the molecular mechanisms by which the three pathways (systems I, II, III) covalently attach heme to the protein (apocytochrome c). These systems are diagrammed on the home page. We use a combination of molecular genetics and membrane protein biochemistry to elucidate, for example, how heme moves through each system and is ultimately attached. Some of the tools we employ and details on assembly are described in the research links on this page.

We are also interested in finding chemical inhibitors of these pathways, since systems I and II are used by prokaryotes, yet humans use the simple, unrelated system III. We discovered that metal (non-iron) porphyrins specifically inhibit systems I and II, and we are developing high throughput screens for the assembly pathways (to discover new inhibitors).

Publications

  1. Gupta D, Sutherland MC, Rengasamy K, Meacham JM, Kranz RG, Bose A.  Photoferrotrophs Produce a PioAB Electron Conduit for Extracellular Electron Uptake.  mBio. 2019 Nov 5;10(6). pii: e02668-19. doi: 10.1128/mBio.02668-19.PMID: 31690680
  2. Sutherland MC, Jarodsky JM, Ovchinnikov S, Baker D, Kranz RG.  Structurally Mapping Endogenous Heme in the CcmCDE Membrane Complex for Cytochrome c Biogenesis.  Journal of Molecular Biology. 2018; 430(8):1065-1080. NIHMSID: NIHMS952326  PMID: 29518410 PMCID: PMC5889519 (A commentary by Iqbal Hamza on this achievement was commissioned by the JMB editor)
  3. Sutherland MC, Tran NL, Tillman DE, Jarodsky JM, Yuan J, Kranz RG. Structure-Function Analysis of the Bifunctional CcsBA Heme Exporter and Cytochrome c Synthetase. mBio. 2018 Dec 18;9(6). pii: e02134-18. doi: 10.1128/mBio.02134-18.PMID:30563894
  4. Babbitt SE, Hsu J, Mendez DL, Kranz RG. 2017.  Biosynthesis of Single Thioether c-Type Cytochromes Provides Insight into Mechanisms Intrinsic to Holocytochrome c Synthase (HCCS).  Biochemistry. 2017 Jul 5;56(26):3337-3346. doi: 10.1021/acs.biochem.7b00286. Epub 2017 Jun 26.  PMID: 28617588
  5. Mendez DL, Akey IV, Akey CW, Kranz RG.  2017.  Oxidized or Reduced Cytochrome c and Axial Ligand Variants All Form the Apoptosome in Vitro. Biochemistry. 2017 Jun 6;56(22):2766-2769. doi: 10.1021/acs.biochem.7b00309. Epub 2017 May 19.  PMID: 28510448
  6. Mendez DL, Babbitt SE, King JD, D’Alessandro J, Watson MB, Blankenship RE, Mirica LM, Kranz RG. 2017.  Engineered holocytochrome c synthases that biosynthesize new cytochromes c.  Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2235-2240. doi: 10.1073/pnas.1615929114. Epub 2017 Feb 14.  PMID: 28196881
  7. Babbitt SE, Hsu J, Kranz RG. 2016.  Molecular Basis Behind Inability of Mitochondrial Holocytochrome c Synthase to Mature Bacterial Cytochromes: DEFINING A CRITICAL ROLE FOR CYTOCHROME c α HELIX-1. J Biol Chem. 2016 Aug 19;291(34):17523-34. doi: 10.1074/jbc.M116.741231. Epub 2016 Jul 6. PMID: 27387500.
  8. Sutherland MC, Rankin JA, Kranz RG. 2016.  Heme Trafficking and Modifications during System I Cytochrome c Biogenesis: Insights from Heme Redox Potentials of Ccm Proteins.  Biochemistry. 2016 Jun 7;55(22):3150-6. doi: 10.1021/acs.biochem.6b00427. Epub 2016 May 26. PMID: 27198710.
  9. Babbitt SE, Sutherland MC, Francisco BS, Mendez DL, Kranz RG.  2015 Mitochondrial cytochrome c biogenesis: no longer an enigma. Trends Biochem Sci. 2015.  Aug;40(8):446-55.  Review.  PMID: 26073510.  PMCID: PMC4509832.
  10. Babbitt SE, San Francisco B, Mendez DL, Lukat-Rodgers GS, Rodgers KR, Bretsnyder EC, Kranz RG.  2014. Mechanisms of Mitochondrial Holocytochrome c Synthase and the Key Roles Played by Cysteines and Histidine of the Heme Attachment Site, Cys-XX-Cys-His.  J Biol Chem. Oct 17;289(42):28795-807.  PMID: 25170082.  PMCID: PMC4200240.
  11. Babbitt SE, San Francisco B, Bretsnyder EC, Kranz RG. 2014.  Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme.  Biochemistry. 2014 Aug 19;53(32):5261-71. PMID: 25054239.  PMCID: PMC4139152.
  12. San Francisco B, Sutherland MC, Kranz RG.  2014.  The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE.    Mol Microbiol. Mar;91(5):996-1008. PMID: 24397552. PMCID: PMC3959880
  13. San Francisco Band Kranz RG. 2014.  Interaction of HoloCcmE with CcmF in Heme Trafficking and Cytochrome c Biosynthesis. J Mol Biol, Feb 6;426(3):570-85. PMID: 24513106 PMCID: PMC3943652.
  14. San Francisco B, Bretsnyder EC and Kranz RG. 2013. Human mitochondrial holocytochrome c synthase’s heme binding, maturation determinants, and complex formation with cytochrome c. Proc Natl Acad Sci Plus USA. Feb 26;110(9):E788-97. PMID: 23150584.  PMCID: PMC3587199.