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.
2022
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
(submitted)
Vougioukalaki, M., Xu, R., Konstantinidou, M., Eleftheriadis, N., Dömling, A., and Gouridis, G. Global Ras structural analysis and its direct pharmacological targeting
(submitted)
2021
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
2020
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
2019
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
2018
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
2017
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
2016
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
2015
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
2013
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
2010
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
2009
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
2007
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
2005
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