imbb logo for mobile
Giorgos Gouridis

Giorgos Gouridis

IMBB Group Leader
Email address
This email address is being protected from spambots. You need JavaScript enabled to view it.

Our research focuses in understanding the intimate structure-function interconnection in biomolecules. For this, we decrypt at the molecular level their structural dynamics.
Protein structural dynamics occur constantly in living cells enabling every protein to perform its tasks and are finely regulated and orchestrated by binding interactions with their partners and/or their respective substrates. Altered protein dynamics lead to cellular malfunction, disease and death. Thus, monitoring those allows us to derive the molecular etiology of human diseases.
Structural dynamics, apart from revealing how proteins function, they also dictate the means by which proteins evolve to compute distinct functions.

The aim of our group, to understand life and evolution at the molecular level, is persuaded by studying protein folding, binding and dynamics. The folding funnel model that is rooted in the free energy landscape theory is the most widely accepted one to describe all 3 life processes, as the only difference between them is chain connectivity. Our labs’ holly-grail is to: (i) Find the key structural elements and understand how such modulate the depth of the energy valleys, (ii) Understand how such elements modulate the enthalpic-entropic factors to by-pass the transition barriers and ultimately (iii) How these elements vary during evolution to confer distinct functions and substrate specificities.

For this, we are coupling “traditional” biochemical/molecular biology tools to an array of powerful (bio)physical procedures (e.g. smFRET, HDX-MS, ITC) and combine the experimental outcome with molecular dynamic simulations (e.g. Gromacs).

Gouridis G, Muthahari YA, de Boer M, Griffith DA, Tsirigotaki A, Tassis K, Zijlstra N, Xu R, Eleftheriadis N, Sugijo Y, Zacharias M, Dömling A, Karamanou S, Pozidis C, Economou A, Cordes T. (2021) Structural dynamics in the evolution of a bilobed protein scaffold. Proc Natl Acad Sci U S A. 118:e2026165118. 

Gouridis G, Hetzert B, Kiosze-Becker K, de Boer M, Heinemann H, Nürenberg-Goloub E, Cordes T, Tampé R. (2019) ABCE1 Controls Ribosome Recycling by an Asymmetric Dynamic Conformational Equilibrium. Cell Rep. 28:723-734.

Gouridis G, Schuurman-Wolters GK, Ploetz E, Husada F, Vietrov R, de Boer M, Cordes T, Poolman B.(2015) Conformational dynamics in substrate-binding domains influences transport in the ABC importer GlnPQ. Nat Struct Mol Biol. 22:57-64.

Gouridis G, Karamanou S, Sardis MF, Schärer MA, Capitani G, Economou A. (2013) Quaternary dynamics of the SecA motor drive translocase catalysis. Mol Cell. 52:655-666.

Gouridis G, Karamanou S, Gelis I, Kalodimos CG, Economou A. (2009) Signal peptides are allosteric activators of the protein translocase. Νature 462:363-367.

Krishnamurthy, S., Sardis, M.F., Eleftheriadis, N., Chatzi, K., Smit, J.H., Karathanou, K., Gouridis, G., Portaliou, A., Bondar, A.N., Karamanou S., Economou, A. Preproteins couple the intrinsic dynamics of SecA to its ATPase cycle to translocate via a catch and release mechanism
(submitted, biorxiv, doi: 10.1101/2021.08.31.458331)

Muthahari, Y., Tsirigotaki, A., Krishnamurthy, S., Hertadi, R., Pozidis, C., and Gouridis, G. The evolution of allosteric networks revealed by an integrative analysis on an ancestral bilobed protein scaffold

Vougioukalaki, M., Xu, R., Konstantinidou, M., Eleftheriadis, N., Dömling, A., and Gouridis, G. Global Ras structural analysis and its direct pharmacological targeting

Gouridis, G., Muthahari, Y., de Boer, M., Griffith, D.A., Tsirigotaki, A., Tassis, K., Zijlstra, N., Xu, R., Eleftheriadis, N., Sugijo, Y., Zacharias, M., Dömling, A., Karamanou, S., Charalambos, P., Economou, A., and Cordes T. Structural dynamics in the evolution of a bilobed protein scaffold
PNAS 118(49):e2026165118

Ploetz, E., Schuurman-Wolters, G.K., Zijlstra, N., Jager, A.W., Griffith, D.A., Guskov, A., Gouridis, G., Poolman, B., and Cordes, T. (2021). Structural and biophysical characterization of the tandem substrate binding domains of the ABC importer GlnPQ
Open biology 11: 200406

Krishnamurthy, S., Eleftheriadis, N., Karathanou, K., Smit, J.H., Portaliou, A., Chatzi, K., Sardis, M.F., Karamanou S., Bondar, A.N., Gouridis, G., and Economou, A. (2021). A nexus of intrinsic dynamics underlies translocase priming
Structure 29:846-858

Tassis, K., Vietrov, R., de Koning, M., de Boer, M., Gouridis, G., and Cordes, T. (2021). Single-molecule studies on conformational states and dynamics in the ABC importer OpuA.
FEBS Lett 595: 717-734

Zernia, S., van der Helde, N., Galenkamp, N.S., Gouridis, G., and Maglia, G. Interpretation of the current blockades of proteins inside nanopores for real-time metabolome analysis
ACS Nano 14: 2296-2307

de Boer, M., Gouridis, G., Muthahari, Y., and Cordes T. Single-Molecule observation of ligand-binding and protein conformation in FeuA
Biophysical journal 119: 1642-1654

Gouridis, G, Hetzert, B., Kiosze-Becker, K, de Boer, M., Heinemann, H., Nürenberg-Goloub, E., Cordes, T., and Tampe, R. ABCE1 controls ribosome recycling by an asymmetric dynamic conformational equilibrium
Cell reports 28:723-734

de Boer, M., Gouridis, G., Vietrov, R.,  Husada, F., Begg, S.L., Schuurman-Wolters, G.K., Husada, F., Eleftheriadis N., Poolman, B., McDevitt, C., and Cordes T. Conformational and dynamics plasticity in substrate-binding proteins underlies selective transport in ABC importers
eLife 8:pii: 44652

Hellenkamp, B., Schmid, S., (12 authors)., Gouridis, G., (40 authors)., and Hugel, T. Precision and accuracy of single-molecule FRET measurements – a worldwide benchmark study
Nature methods 15: 669-676

Sardis, M.F., Tsirigotaki, A., Chatzi, E.K., Portaliou, G.A., Gouridis, G., Karamanou, S., and Economou, A. Preprotein conformational dynamics drive bivalent translocase docking and secretion
Structure 25: 1056-67
See comment in faculty of 1000 by Karin Roemisch

van der Velde, J.H., Oelerich, J., Huang, J., Smit, J.H., Aminian Jazi, A., Galiani, S., Kolmakov, K., Gouridis, G., Eggeling, C., Herrmann, A., Roelfes, G. and Cordes, T. A simple and versatile design concept for fluorophore derivatives with intramolecular photostabilization.
Nature Communications 7: 10144

Husada, F., Gouridis, G., Vietrov, R., Schuurman-Wolters, G.K., Ploetz, E., de Boer, M., Poolman, B. and Cordes, T. Watching conformational dynamics of ABC transporters with single-molecule tools.
Biochemical Society Transactions 43: 1041-7

Gouridis, G., Schuurman-Wolters, G.K., Ploetz, E., Husada, F., Vietrov, R., de Boer, M., Cordes, T. and Poolman, B. Conformational dynamics in substrate-binding domains influences transport in the ABC importer GlnPQ.
Nature Structural & Molecular Biology 22: 57-64

Gouridis, G., Karamanou, S., Sardis, M.F., Schärer, M.A., Capitani, G. and Economou, A. Quaternary dynamics of the SecA motor drive translocase catalysis.
Molecular Cell. 52: 655-66

Gouridis, G., Karamanou, S., Koukaki, M. and Economou, A. In vitro assays to analyze translocation of the model secretory preprotein alkaline phosphatase.
Methods in Molecular Biology 619, 157-72

Gouridis, G., Karamanou, S., Gelis, I., Kalodimos, C.G., and Economou, A. (2009) Signal peptides are allosteric activators of the protein translocase.
Νature 462, 363-36

Gelis, I., Bonvin, A.M.J.J., Keramisanou, D., Koukaki, M., Gouridis, G., Karamanou, S., Economou, A. and Kalodimos, C.G. (2007) Structural Basis for Signal-Sequence Recognition by the Translocase Motor SecA as Determined by NMR
Cell 131, 756-769
See comment from Faculty of 1000; see presentation by Thireos et al., 2008

Karamanou, S., Gouridis, G., Papanikou, E., Sianidis, G., Gelis, I., Keramisanou, D., Vrontou, E., Kalodimos, C.G., and Economou, A. (2007) Preprotein-controlled catalysis in the helicase motor of SecA.
EMBO Journal 26, 2904-2911
See comment from Faculty of 1000; see article in LabTimes

Karamanou, S., Sianidis, G., Gouridis, G., Pozidis C., Papanikolau, Y., Papanikou, E., and Economou, A. (2005) E. coli SecA truncated at its termini is functional and dimeric.
FEBS Letters 579, 1267-1271