Currently not accepting new graduate students
- Member - Turkish Academy of Science
- Fellow - American Academy of Microbiology
- Fellow - American Association for the Advancement of Science
- DAAD Alumnus
photosynthetic and respiratory electron transfer pathways and structure, function and biogenesis of cytochrome complexes
We are interested in understanding the molecular basis of biological electron transfer during cellular energy tranduction in photosynthesis and respiration. These basic metabolic pathways contain several multisubunit, membrane-bound protein complexes with various redox-active prosthetic groups. They are vital components for important cellular functions ranging from ATP synthesis to secretion, solute transport, motility and thermogenesis. Their dysfunction severely compromises cellular energy production, and leads to low crop yields in plants (photosynthesis), or neurological and muscular diseases in humans (respiration). A detailed understanding of how these evolutionarily well-conserved energy producing molecular machines perform their functions is of considerable biological significance and of general interest. Our studies aim to define the structure, function, assembly, biogenesis and regulation of these proteins in response to environmental signals, such as light and oxygen. Cytochrome bc1 complex and cytochrome cbb3 oxidase, which are membrane-associated proton bumps, and their physiological electron carriers the cytochromes c2 and cy are currently under study.
Figure 1. Overview of Cu delivery pathway to cbb3-type cytochrome c oxidase. Environmental copper (Cu) is imported into the cytoplasm by CcoA, and on its way is likely to be reduced by CcoG, and then conveyed to CopZ, a cytoplasmic Cu chaperone. CopZ donates Cu to two P1B type Cu-ATPases, Ccol for biosyntesis of cbb3-type cytochrome c oxidase, and to CopA for detoxification and cellular Cu homeostasis. Periplasmi Cu chaperones PccA and SenC work together to ultimately convery Cu to the CcoN subunit of the cbb3-type cytochrome c oxidase during its biogenesis? Refers to steps that are under investigation.
We use molecular genetic and genomic approaches combined with biochemical, biophysical and structural techniques. As a model system, we use the purple non-sulfur photosynthetic bacterium Rhodobacter capsulatus instead of mitochondria of eukaryotes or chloroplasts of plants which are more refractory to multidisciplinary analyses. Current work is focused on the 1) structure and function of the functional sites of the cytochrome complexes and the assembly of their subunits and 2) biogenesis of c-type cytochromes including cyt cy and cyt cbb3 which are novel membrane-associated electron carriers recently discovered in our group.
Figure 2. Overview of cytochrome c maturation System I (CcmABCDEFGHI) supercomplex. Apocytochromes c are translated in the cytoplasm and excreted to the periplasm via the Sec translocon. They are exposed to the oxidative folding pathway for proteins (DsbA and DsbB) to gain their disulfide bond at their conserved CysXxxXxxCysHis heme ligation motifs. This disulfide bond is reduced by the thioreductive pathway (CcdA and CcmG), and reduced apocytochromes c are trapped via thier C-terminal ends by Ccml. Subsequently they form a mixed disulfide bond with CcmH in a stereospecific manner to allow the thioether bond formation by the heme ligation complex CcmFHI between their free C-terminal Cys and the vinyl-4 of heme held by CcmE. Concurently, heme is biosynthesized on the inner surface of the cytoplasmic membrane, and translocated to the periplasm vis the CcmABCD comples, and attached to CcmE via CcmC though its vinyl-2 group. The heme chaperone CcmE conveys heme to the ligation complex to catalyze the two thioether bonds, first between the C-terminal Cys and vinyl-4 and then the N-terminal Cys and vinyl-2 of heme yield sterospecific covalent hem ligation to apocytochrome c. Matured cytochrome c then undergoes folding to reach its native and functional form.
- BIOL 401 - Prokaryotic Microbiology
- BIOL 101 - Introductory Biology
Microbial Energy Transduction: Genetics, Structure and Function of Membrane Proteins. 1986. D. C. Youvan and F. Daldal, Eds. Cold Spring Harbor Laboratory Press, NY., USA.
The Purple Phototrophic Bacteria. 2008. C. N. Hunter, F. Daldal, M. C. Thurnauer and J. T. Beatty, Eds. Springer, Dordrecht, The Netherlands.
Selected Recent Publications (2014-2018):
Ekici, S., Turkarslan, S., Pawlik, G., Dancis, A., Baliga, N., Koch, H-G. and Daldal, F. (2014). Intracytoplasmic copper homeostasis controls cytochrome c oxidase production. MBio, 5: 1055-13. PMID: 2445735.
Verissimo, A. F. and Daldal, F. (2014) Cytochrome c maturation: an intricate process catalyzed by a supercomplex? Biochim. Biophys Acta Bioenergetics, 1837: 989-998. PMID: 24631867.
Yildiz, G. G., Gennis, R. B., Daldal, F. and Ozturk, M. (2014) The KC-channel in the cbb3-type respiratory oxygen reductase from Rhodobacter capsulatus is required for both chemical and pumped protons. J. Bacteriol. 196: 1825-1832. PMID: 24563037.
Verissimo, A. F., Shroff, N. and Daldal, F. (2015). During Cytochrome c Maturation CcmI Chaperones the Class I Apocytochromes until the Formation of Their b-Type Cytochrome Intermediates. J. Biol. Chem. 290: 16989-7003 . PMID: 25979338
Trasnea, P-I., Utz M., Khalfaoui-Hassani, B., Lagies, S., Daldal, F. and Koch, H-G. (2015). Cooperation between two periplasmic copper chaperones is required for full activity of the cbb3-type cytochrome c oxidase and copper homeostais in Rhodobacter capsulatus. Mol. Micro. 100: 345-61. PMID: 26718481.
Khalfaoui-HAssani, B., Verissimo, A. F., Shroff, N., Ekici, S., Trasnea, P-I, Utz, M., Koch, H-G, and Daldal, F. (2016) Biogensesis of cytochrome c complexes: from insertion of redox cofactors to assembly of different subunits, pp. 527-555. In Cytochrome Complexes: Evolution, Structures, Energy Transduction, and Signaling. Cramer, W. and Kallas, T. (Editors), Springer Dordrecht
Khalfaoui-Hassani, B., Verissimo, A. F., Koch, H-G, and Daldal, F. (2016). Uncovering the Transmembrane Metal Binding Site of the Novel Bacterial MFS-type Copper Importer CcoA. MBio. 7: 1981-15. PMID: 26787831
Francia, F., Malferrari, M., Lanciano, P., Daldal, F. and Venturoli, G. (2016). The Cytochrome b Zn binding Amino Acid Residue Histidine 291 is Essential for Ubihydroquinone Oxidation at the Qo Sute of Bacterial Cytochrome bc1. Biochim. Biophys Acta-Bionergetics 1857: 1796-1806. PMID: 27550309
Vos, M. H., Reeder, B. J., Daldal, F. and Liebl, U. (2017). Ultrafast photochemistry of the bc1 complex. Phy. Chem. Chem. Phys. 19: 6807-6813. PMID: 28218331 and correction.
Verissimo AF, Khalfaoui-Hassani B, Hwang J, Steimle S, Selamoglu N, Sanders C, Khatchikian CE, Daldal F. (2017). The thireduction component CcmG confers efficiency and the hem ligation component CcmH ensures stereo-specificty during cytochrome c maturation. J. Biol. Chem. 292: 13154-13167. PMID: 28634234
Onder, O., Verissimo, AF., Khalfaoui-Hassani, B., Peters, A., Koch, H-G. and Daldal, F. (2017). Absence of thiol-disulfide oxidoreductase DsbA impairs cbb3-type cytochrome c oxidase biogenesis in Rhodobacter capsulatus. Fron. Microbial. 8: 2576. PMID:29312253
Tropeano, CV., Fiori, J., Carelli, V. Caporali, L., Daldal, F., Ghelli, AM and Rugolo, M. (2018). Complex II phosphrylation is triggered by unbalanced redox homeostasis in cells lacking Complex III. Biochim Biophys Acta Bioenergetics, 1859: 182-190. PMID: 29269267 and corrigendum.
Khalfaoui-Hassani, B., Wu, H., Blaby-Haas, C., Zang, Y., Sandir, F., Verissimo, AF., Koch, H-G. and Daldal, F. (2018). Widespread distribution and functional specificity of the copper imprter CcoA: Separate copper uptake and delivery routes to bacterial cytochrome c oxidases. MBio, 9: e00065-18. PMID: 29487231
Sandri, F., Musiani, F., Selamogly, N., Daldal, F. and Zannoni, D. (2018). Pseudomonas pseudoalcaligenes KF707 grown with biphenyl expresses a caa3 type cytochrome c oxidase. FEBS Lett 1873: 3468- PMID: 29427514
Trasnea, P-I., Andreei, A., Marckmann, D, Utz, M., Khalfaoui-HAssani, B., Daldal, F. and Koch, H-G. (2018). Copper tranfer between two periplasmic copper chaperones involved in Rhodobacter capsulatus cbb3-type cytochrome oxidase biogenesis. ACS Chem. Biol. 13: 1388-1397. PMID: 29613755