Efstratios Mylonas

Jul 23, 2024


Assistant Professor (male)
X3-104
Organic Chemistry and Biochemistry
Department of Chemistry
University of Ioannina

 e-mail: mylonas[at]uoi.gr
 Tel: +30 265100 8368
 Fax:

https://www.scopus.com/authid/detail.uri?authorId=14621741600
https://www.scopus.com/authid/detail.uri?authorId=14621741600
https://scholar.google.com/citations?user=IZyfr6IAAAAJ

Biochemistry



Research interests

My main research interests lie in the structural characterization of biological macromolecules and subsequently the functional implications/consequences of these structures. Understanding the function of biological macromolecules requires knowledge of their three dimensional arrangement and organization which can provide crucial information for their role in the cell, e.g. enzymatic activity, protein/nucleic acid interactions, metabolic pathways etc. Moreover, the Protein Folding Problem, i.e. the “translation” of the sequence to a 3D structure is fundamental in Biosciences.

More specifically, my current research activity focuses on the following projects:

Understanding the regulation of the Type III Secretion System of bacterial pathogens. Type III Secretion System (T3SS) is used by Gram-negative bacteria to infect a broad range of animal (including humans) and plant (including economically significant crops) hosts. T3SS is evolutionary related to flagella and is a large molecular machine that injects the host cytoplasm with proteins that facilitate the survival of the bacteria, e.g. by suppressing the host immune system. On the other hand, T3SS is “expensive” for the bacterial cell to deploy and needs to be tightly regulated at both the protein expression and secretion level. Plant pathogen Pseudomonas syringae and Erwinia amylovora T3SS consists of ~30 core proteins with structural or regulatory role. My objective is to decipher the network of interactions that governs the activation of T3SS through the biochemical, structural and functional characterization of T3SS core proteins and protein complexes and characterize the interplay with other bacterial processes.

Rational protein design. The accumulated structural knowledge over the last decades as well as recent advances in,  Artificial Intelligence-powered, protein structure prediction tools have rendered the prospect of creating protein/enzymes with improved or new properties and features more attainable than ever. This can be realized by targeted mutations in existing proteins, by combining features of multiple proteins, e.g. by merging the catalytic domain of one with the subcellular localization or DNA-binding domain of another or even by de novo design of proteins of desired shape and activity. Structural information is extremely valuable as it affords us their rational design in silico before attempting to produce them experimentally. It is even possible to predict the folding of artificial proteins and manipulate the catalytic specificity of enzymes. My goal is the rational protein design and production of proteins with new, desirable, properties (e.g. endonucleases) for Biotechnological and Biomedical applications.

 

Publications

(Total: 25 – Citations[excluding self-citations]: 2197 – h-index: 17 – source: SCOPUS)

 

  • Makraki E., Miliara S., Pagkalos M., Kokkinidis M., Mylonas E.*, Fadouloglou V.E. (2023) Probing the conformational changes of in vivo overexpressed cell cycle regulator 6S ncRNA. Front Mol Biosci, 10, 1219668. (*Corresponding author)
  • Ferrari M.L., Charova S.N., Sansonetti P.J., Mylonas E.*, Gazi A.D. (2021) Structural Insights of Shigella Translocator IpaB and Its Chaperone IpgC in Solution. Front Cell Infect Microbiol, 11, 673122. (*Corresponding author)
  • Kefala A., Amprazi M., Mylonas E., Kotsifaki D., Providaki M., Pozidis C., Fotiadou M., Kokkinidis M. (2021) Probing Protein Folding with Sequence-Reversed α-Helical Bundles. Int J Mol Sci, 22(4), 1955.
  • Khalid R.R., Maryam A., Sezerman O.U., Mylonas E., Siddiqi A.R., Kokkinidis M. (2020) Probing the Structural Dynamics of the Catalytic Domain of Human Soluble Guanylate Cyclase. Sci Rep, 10, 9488.
  • Mylonas E., Yagi N., Fujii S., Ikesue K., Ueda T., Moriyama H., Sanada Y., Uezu K., Sakurai K., Okobira T. (2019) Structural analysis of a calix[4]arene-based Platonic Micelle. Sci Rep, 9, 1982.
  • Khalid R.R., Siddiqi A.R., Mylonas E., Maryam A., Kokkinidis M. (2019) Dynamic Characterization of the Human Heme Nitric Oxide/Oxygen (HNOX) Domain under the Influence of Diatomic Gaseous Ligands. Int J Mol Sci, 20(3), 698.
  • Charova S.N., Gazi A.D., Mylonas E., Pozidis C., Sabarit B., Anagnostou D., Psatha K., Aivaliotis M., Beuzon C.R., Panopoulos N.J., Kokkinidis M. (2018) Migration of Type III Secretion System Transcriptional Regulators Links Gene Expression to Secretion. mBio, 9(4), e01096-18.
  • Fujii S., Yamada S., Matsumoto S., Kubo G., Yoshida K., Tabata E., Miyake R., Sanada Y., Akiba I., Okobira T., Yagi N., Mylonas E., Ohta N., Sekiguchi H., Sakurai K. (2017). Platonic Micelles: Monodisperse Micelles with Discrete Aggregation Numbers Corresponding to Regular Polyhedra. Sci Rep, 7, 44494.
  • Sanada Y., Sakamoto S., Shiomi T., Okobira T., Mylonas E., Ohta N., Yagi N., Nishikawa M., Akiba I., Takakura Y., Sakurai K. (2014). X-ray scattering from immunostimulatory tetrapod-shaped DNA in aqueous solution to explore its biological activity-conformation relationship. J Phys Chem B, 118(35), 10373-10379.
  • Nishimura T., Sanada Y., Matsuo T., Okobira T., Mylonas E., Yagi N., Sakurai K. (2013). A bimolecular micelle constructed from amphiphilic pillar[5]arene molecules. Chem Commun (Camb), 49(29), 3052-3054.
  • Sanada Y., Akiba I., Sakurai K., Shiraishi K., Yokoyama M., Mylonas E., Ohta N., Yagi N., Shinohara Y., Amemiya Y. (2013). Hydrophobic molecules infiltrating into the poly(ethylene glycol) domain of the core/shell interface of a polymeric micelle: evidence obtained with anomalous small-angle X-ray scattering. J Am Chem Soc, 135(7), 2574-2582.
  • Fujii, S., Sanada, Y., Nishimura, T., Akiba, I., Sakurai, K., Yagi, N., Mylonas, E. (2012). A stimulus-responsive shape-persistent micelle bearing a calix[4]arene building block: reversible pH-dependent transition between spherical and cylindrical forms. Langmuir, 28(6), 3092-3101.
  • Bertini, I., Fragai, M., Luchinat, C., Melikian, M., Mylonas, E., Sarti, N., Svergun, D.I. (2009). Interdomain flexibility in full-length matrix metalloproteinase-1 (MMP-1). J Biol Chem, 284(19), 12821-12828.
  • Zeev-Ben-Mordehai, T., Mylonas, E., Paz, A., Peleg, Y., Toker, L., Silman, I., Svergun, D.I., Sussman, J.L. (2009). The quaternary structure of amalgam, a Drosophila neuronal adhesion protein, explains its dual adhesion properties. Biophys J, 97(8), 2316-2326.
  • Mylonas, E., Hascher, A., Bernadó, P., Blackledge, M., Mandelkow, E. and Svergun, D.I. (2008). Domain Conformation of Tau Protein Studied by Solution Small-Angle X-ray Scattering. Biochemistry, 47, 10345-10353.
  • Shukla, A., Mylonas, E.*, Di Cola, E., Finet, S., Timmins, P., Narayanan, T. and Svergun, D.I. (2008). Absence of equilibrium cluster phase in concentrated lysozyme solutions. Proc Natl Acad Sci U S A, 105, 5075-5080. (*First co-author)
  • Bertini, I., Calderone, V., Fragai, M., Jaiswal, R., Luchinat, C., Melikian, M., Mylonas, E. and Svergun, D.I. (2008). Evidence of reciprocal reorientation of the catalytic and hemopexin-like domains of full-length MMP-12. J Am Chem Soc, 130, 7011-7021.
  • Wells, M., Tidow, H., Rutherford, T.J., Markwick, P., Jensen, M.R., Mylonas, E., Svergun, D.I., Blackledge, M. and Fersht, A.R. (2008). Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain. Proc Natl Acad Sci U S A, 105, 5762-5767.
  • Paz, A., Zeev-Ben-Mordehai, T., Lundqvist, M., Sherman, E., Mylonas, E., Weiner, L., Haran, G., Svergun, D.I., Mulder, F.A.A., Sussman, J.L. and Silman, I. (2008). Biophysical characterization of the unstructured cytoplasmic domain of the human neuronal adhesion protein neuroligin 3. Biophys J, 95, 1928-1944.
  • Mylonas, E. and Svergun, D.I. (2007). Accuracy of molecular mass determination of proteins in solution by small-angle X-ray scattering. J Appl Cryst, 40, s245-s249.
  • Bernadó, P., Mylonas, E., Petoukhov, M.V., Blackledge, M. and Svergun, D.I. (2007). Structural Characterization of Flexible Proteins Using Small-Angle X-ray Scattering. J Am Chem Soc, 129, 5656-5664.
  • Tidow, H., Melero, R., Mylonas, E., Freund, S.M.V., Grossmann, J.G., Carazo, J.M., Svergun, D.I., Valle, M. and Fersht, A.R. (2007). Quaternary structures of tumor suppressor p53 and a specific p53 DNA complex. Proc Natl Acad Sci U S A, 104, 12324-12329.
  • King-Scott, J., Nowak, E., Mylonas, E., Panjikar, S., Roessle, M., Svergun, D.I. and Tucker, P.A. (2007). The structure of a full-length response regulator from Mycobacterium tuberculosis in a stabilized three-dimensional domain-swapped, activated state. J Biol Chem, 282, 37717-37729.
  • Marx, A., Nugoor, C., Müller, J., Panneerselvam, S., Timm, T., Bilang, M., Mylonas, E., Svergun, D.I., Mandelkow, E. and Mandelkow, E. (2006). Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2. J Biol Chem, 281, 27586-27599.
  • Platsoucas, C.D., Lu, S., Nwaneshiudu, I., Solomides, C., Agelan, A., Ntaoula, N., Purev, E., Li, L.P., Kratsios, P., Mylonas, E., Jung, W., Evans, K., Roberts, S., Lu, Y., Layvi, R., Lin, W.L., Zhang, X., Gaughan, J., Monos, D.S., Oleszak, E.L. and White, J.V. (2006). Abdominal aortic aneurysm is a specific antigen-driven T cell disease. Ann N Y Acad Sci, 1085, 224-235.



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