Fevzi Daldal, Ph. D. Professor of Biology 103B Carolyn Lynch Laboratory Department of Biology University of Pennsylvania Philadelphia, PA 19104 USA V +1 215 898.4394 F +1 215 898.8780 E fdaldal@sas.upenn.edu

Fevzi Daldal    (TIFF, ~0.5 MB)

research : publications : education : awards : teaching

photosynthetic and respiratory electron transfer pathways and structure, function and biogenesis of cytochrome complexes figure 1 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.

selected publications (2001-2007) Sanders, C., C. Boulet and F. Daldal. (2007) Membrane-spanning and periplasmic segments of CcmI have distinct functions during cytochrome c biogenesis in Rhodobacter capsulatus. J Bacteriol., in press. Onder, O., Yoon, H., B. Naumann, M. Hippler, A. Dancis and F. Daldal. (2006) Modifications of the lipoamide-containing mitochondrial subproteome in a yeast mutant defective in cysteine desulfurase, Mol Cell Proteomics, 5: 1426-1436. Aygun, S., S. Mandaci, H-G. Koch, H. Goldfine and F. Daldal. (2006) Ornithine lipids are required for membrane cytochrome complexes. Molec. Microbiol. 61: 418-435. Lee. D-W., Y. Ozturk, A. Mamedova, A., Osyczka, J. W. Cooley and F. Daldal. (2006) A functional hybrid between the cytochrome bc1 complex and its physiological membrane anchored electron acceptor cyt cy in R. capsulatus. Biochim. Biophys. Acta, 1757: 346-352. Turkarslan, S., Sanders, C. and F. Daldal. (2006) Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c-type cytochromes. Molec. Microbiol. 60: 537-541. Kulajta, C., J. O. Thumfart, S. Haid, F. Daldal and Koch, H-G. (2006) Multi-step assembly pathway of the cbb3-type cytochrome c oxidase complex. J. Mol. Biol. 355: 989-1004. Sanders, C., M. Deshmukh, D. Astor, R. G. Kranz and F. Daldal. (2005) Overproduction of CcmG and CcmFHRc fully suppresses the c-type cytochrome biogenesis defect of R. capsulatus CcmI-null mutants. J. Bacteriol. 187: 4245-4256. Berry, E. A., L-S. Huang, N. G.,Pon, Valkova- Valchanova, M. , and F. Daldal. (2004) X-ray structure of Rhodobacter capsulatus cytochrome bc1: Comparison with its mitochondrial and chloroplast counterparts. Photosyn. Res., 81: 251-275. Osyczka, A., C. C. Moser, F. Daldal, and P. L. Dutton. (2004) Selective cofactor knockout reveals primary catalytic unit of cytochrome bc1. Nature, 427: 607-612. Darrouzet, E. and F. Daldal. (2003) Protein-protein interactions between cytochrome b and the Fe-S protein subunits during QH2 oxidation and the large-scale domain movement in the bc1 complex. Biochemistry, 42:1499-1507. Deshmukh, M., Turkarslan, S., Astor, D., Valkova-Valchanova, M. and F. Daldal. (2003) The dithiol:disulfide oxidoreductases DsbA and DsbB of Rhodobacter capsulatus are not directly involved in cyt c biogenesis but their inactivation restores the cyt c biogenesis defect of CcdA-null mutants. J. Bacteriol. 185: 3361-3372. Katzen, F., M. Deshmukh, F. Daldal and J. Beckwith. (2002) Evolutionary domain fusion expanded the substrate specificity of the transmembrane electron transporter DsbD. EMBO J. 21: 3960-3969. Deshmukh, M., M. May, Y. Zhang, K. Gabbert, K. A. Karberg, R. G. Kranz and F. Daldal. (2002) Over expression of ccl1-2 can bypass the need for the putative apocytochrome chaperone CycH during the biogenesis of c-type cytochromes. Molec. Micro 46: 1069-1080. Darrouzet, E. and F. Daldal. (2002) Movement of the Fe-S subunit beyond the ef loop of cytochrome b is required for multiple turnovers of the bc1 complex but not for single turnover Qo site catalysis. J. Biol. Chem. 277: 3464-3470, and 3471-3476. Darrouzet, E., C. C. Moser, P. L. Dutton and F. Daldal. (2001) Large scale domain movement in cytochrome bc1: a new device for electron transfer in proteins. Trends in Biochemical Sciences, 26: 445-451.

education Ph.D., University of Strasbourg, France Post-Doc., Harvard Medical School Scientist, Cold Spring Harbor Laboratory

awards Member - Turkish Academy of Science Fellow - American Academy of Microbiology

teaching BIOL 475 - Microbiology and Biotechnolgoy BIOL 101 - Introductory Biology