photosynthetic and respiratory electron transfer pathways and structure, function and biogenesis of cytochrome complexes
A schematic drawing of the photosynthetic and respiratory electron transport pathways and components of the facultative phototrophic bacterium Rhodobacter capsulatus. Download full (high-quality) PDF drawing.
We are interested in understanding the molecular basis of biological electron transfer during cellular energy transduction 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 pumps, and their physiological electron carriers the cytochromes c2 and cy are currently under study.
figure 2 - Ccm-system I components for c-type cytochrome maturation in purple bacteria.
All components of the c-type cyt maturation, except the thiol-disulfide oxidoreductase DsbA, are located in the cytoplasmic membrane. Both apocyt c and heme follow different routes to the heme ligation core complex, composed of CcmI, CcmH and CcmF. Apocyt c is translocated via the Sec pathway, its cysteine thiols in the conserved CXYCH motif are first oxidized by the DsbA- DsbB pathway, and then reduced by the cyt c maturation specific CcdA - CcmG and/or CcmH thio-reductive pathway. CcmI is involved in delivering apocyt c to the core heme ligation complex via its different domains. Heme is translocated across the membrane, possibly via ABCtype transporter CcmABCD, and is covalently attached to the conserved His residue of the heme chaperone CcmE. CcmC is involved in attaching heme to CcmE, and CcmD enhance holo-CcmE production. CcmA and CcmB promote the release of holo-CcmE from CcmC and CcmD. Upon formation of the thioether bonds between the apocyt c and heme vinyls, catalyzed by CcmH, CcmI and CcmF complex mature holocyt c is released. Download full (high-quality) PDF drawing.
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.
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 (2009-2012):
Cooley, J. W., Lee, D-W. and F. Daldal (2009). Across membrane communication between the Qo and Qi active sites of cytochrome bc1, Biochemistry, 48: 1888-1899.
Onder, O., Aygun-Sunar, S., Selamoglu, N. and F. Daldal (2010). A glimpse into the proteome of photorophic bacterium R. capsulatus. Adv Exp Med Biol. 675:179-209. PMID: 20532742
Sanders, C., Turkarslan, S., D-W. Lee and F. Daldal. (2010). Cytochrome c biogenesis: The Ccm system. Trends Microbiol. 18:266-74. PMID: 20382024
Pawlik, G., Kulajta, C., Sachelaru, I., Schröder, S., Waidner, B., Hellwig, P., Daldal, F. and Koch, H-G. (2010). The putative assembly factor CcoH is stably associated with the cbb3-type cytochrome oxidase. J. Bacteriol. 192: 6378-89. PMID: 20952576
Sarry, J-E., Lyver , E., Micklow , E., Deutsch, E., Onder, O., Selamoglu, N., Yager, C., Knight, S., Daldal, F., Dancis, A.,Lynch, D. D. and Selak, M. A. (2011). Blood cells from Friedreich ataxia patients harbor frataxin deficiency without a loss of mitochondrial function. Mitochondrion 11: 342-350. PMID: 21147271
Lanciano, P., Lee, D-W., Yang, H., Darrouzet, E. and F. Daldal. (2011). Inter-monomer electron transfer between the low potential b hemes of cytochrome bc1. Biochemistry, 50: 1651-1663. PMID: 21261281
Lee, D-W., Selamoglu, N., Lanciano, P., Cooley, J. W., Forquer, I., Kramer, D. and F. Daldal. (2011). Loss of a conserved tyrosine residue of cytochrome b induces reactive oxygen species production by cytochrome bc1. J. Biol. Chem. 286: 18139-18148. PMID: 21454570
Lee, D-W., Khoury, Y.E., Francia, F., Zambelli, B., Ciurli, S., Venturoli, G., Hellwig, P. and F. Daldal. (2011). Zinc inhibition of bacterial cytochrome bc1 reveals the role of cytochrome b E295 in proton release at the Qo site. Biochemistry, 50: 4263-4272. PMID: 21500804
Verissimo, A.F., Yang, H., Wu, X., Sanders, C. and F. Daldal. (2011). CcmI subunit of CcmFHI heme ligation complex functions as an apocytochrome c chaperone during c-type cytochrome maturation. J. Biol Chem. 286: 40452-40463. PMID: 21956106
Ekici, S., Pawlik, G., Lohmeyer, E., Koch, H-G. and F. Daldal. (2012). Biogenesis of cbb3-type cytochrome c oxidase in Rhodobacter capsulatus. Biochim. Biophys Acta Bioenergetics, 1817: 898-910. PMID: 22079199
Ekici, S., Yang, H., Koch, H-G. and F. Daldal. (2012). A novel transporter required for biogenesis of cbb3-type cyt c oxidase in Rhodobacter capsulatus. mBio, 3: 293-311. PMID: 22294680
Khalfaoui-Hassani, B., Lanciano, P., Lee, D-W., Darrouzet, E. and F. Daldal. (2012). Recent advances in cytochrome bc1: Inter monomer electronic communication? FEBS Letts. 586: 617-621. PMID: 21878327
Verissimo, A., Sanders, J., Daldal, F. and C. Sanders. (2012). Engineering a prokaryotic apocytochrome c as an efficient substrate for Saccharomyces cerevisiae cytochrome c heme lyase. Biochim. Biophys. Res. Com. 424: 130-135. PMID: 22732413
Lohmeyer, E., Schroder, S., Pawlik, G., Trasnea, P-I, Peters, A., Daldal, F. and H-G. Koch. (2012). The copper binding ScoI homologue SenC binds directly to the cbb3-type cytochrome oxidase in Rhodobacter capsulatus. Biochim Biophys Acta. 1817: 2005-2015. PMID: 22771512
Ekici, S., Wu. X., Jian X. Koch, H-G. and F. Daldal. (2012). Missense mutations in cytochrome c maturation genes provide new insights on Rhodobacter capsulatus cbb3-type cytochrome oxidase biogenesis. J Bacteriol. 195: 261-269. PMID: 23123911
Verissimo, A. F., Mohtar, M. A. and F. Daldal. (2013). The heme chaperone apoCcmE forms a ternary complex with CcmI and apocytochrome c. J. Biol. Chem. 288: 6272-6283. PMID: 23319598.
Ghelli, A., Marchesini, A., Tropeano, C. V., Calvaruso, M. O., Iommarini, L., Porcelli, A. M.,. Zanna, C., Nardo, V. D., Martunizzi, A., Wibrand, F., Vissing, J., Kurelac, I., Gasparre, G., Selamoglu, N., Daldal, F. and M. Rugolo. (2013). The cytochrome b p.278y>c mutation causative of a multisystem disorder enhances superoxide production and alters supramolecular interactions of respiratory chain complexes. Hum. Mol. Genet, 22: 2141-51. PMID: 23418307.
Lanciano, P., Khalfaoui-Hassani, B., Ghelli, A., Rugolo, M. and Daldal, F. Molecular mechanisms of superoxide production by complex III: A bacterial versus human mitochondrial comparative case study (2013). Biochim. Biophys Acta Bioenergetics, in press. PMID: 23542447.
- Member - Turkish Academy of Science
- Fellow - American Academy of Microbiology
- Fellow - American Association for the Advancement of Science
- DAAD Alumnus
Cell and Molecular Biology Graduate Group -http://www.med.upenn.edu/camb/faculty/mv/daldal.html
Biochemistry and Molecular Biophysics Graduate Group -http://www.med.upenn.edu/bmbgrad/Faculty/Master_List/Daldal/daldal.html
Daldal Research Group -