My laboratory uses macromolecular crystallography and other structural biology techniques in the study of biological processes . We have published approx. 100 research papers and coordinated several transnational research projects.
- Structural studies of DNA binding proteins, e.g. restriction endonucleases (R. Pvu II), mammalian (DNMT1, DNMT3) and bacterial ( Bse CI) DNA methyltransferases and of RNA-binding proteins (Rop) have been performed. Applications resulting from this work include the engineering of “programmable” endonucleases and novel DNA specificities for gene therapy and endonucleases which are controllable by light.
- Gram negative bacteria deploy various secretion systems for exporting proteins to eukaryotic hosts. We study the Type III secretion systems (T3SS) which are directly related to pathogenicity and essential mediators of the interactions between bacteria and eukaryotes . We have determined the first crystal structure of a conserved core T3SS protein (HrcQ B ) and performed the first characterization by SAXS of an intrinsically disordered, highly interactive protein (HrpO). Numerous studies of TTSS protein complexes are in progress.
- We have made fundamental contributions to protein folding/stability with a focus on helical bundle proteins and applications resulting in the development of innovative, bio-inspired materials.
- Other crystallographic projects target bacterial resistance to antibiotics, deacetylases, etc.
Athanasiadis, A., Vlassi, M., Kotsifaki, D., Tucker, P., Wilson , K.S. and M. Kokkinidis, The crystal structure of Pvu II endonuclease reveals extensive structural homologies to Eco RV. Nature, Struct. Biol. 1, 469-475 (1994)
Gogos, J., Jin Jingmin, Wan, H., Kokkinidis, M. and Kafatos, F.C., Recognition of diverse Sequences by Class I Zinc Fingers: Asymmetries and indirect effects on specificity in the interaction between CF2II and A+T-rich sequence elements, Proc. Natl. Acad. Sci. USA 93, 2159-2164 (1996)
V.E. Fadouloglou, A.P. Tampakaki, N.M. Glykos, M.N. Bastaki, J.M. Hadden, S.E. Phillips, N.J. Panopoulos and M. Kokkinidis, Structure of HrcQ B -C, a conserved component of the bacterial type III secretion systems, Proc. Natl. Acad. Sci. USA 101, 70-75 (2004)
A. Gazi , M. Bastaki, S.N. Charova, E.A. Gkougkoulia, E.A. Kapellios, N.J. Panopoulos and M. Kokkinidis, Evidence for a coiled-coil interaction mode of disordered proteins from bacterial type III secretion systems, J. Biol. Chemistry, 283: 34062 – 34068 (2008)
B. Schierling, A.-J. Noel, W. Wende, H.L. Tie, E. Kubareva, T. Oretskaya, M. Kokkinidis and A. Pingoud, Controlling the enzymatic activity of a restriction enzyme by light, Proc. Natl. Acad. Sci. USA 107:1361-1366 (2010).