Research interests

• Collective excitation by terahertz fields
  
• Quantum phase transition of atoms is usually associated with extremly low temperatures in well shielded environments. There is a growing evidence that excitonic and vibrational mechanical energy also exhibit bosonic particle behaviour even at ambient temperatures and subject to these phase transitions. Our research focus on the delicate interplay between terahertz phonons and photons in biological systems in their native condensed phase. We are also interested in what biological processes collective excitation play an active role.

  
  
  

  References:

  Lundholm, I.V., Rodilla, H., Wahlgren, W.Y., Duelli, A., Bourenkov, G., Vukusic, J., Friedman, R., Stake, J., Schneider, T. & Katona, G. (2015) Terahertz radiation induces non-thermal structural changes associated with Frohlich condensation in a protein crystal. Structural Dynamics, 2(5), 054702

  Ahlberg Gagner, V., Lundholm, I., Garcia-Bonete, M.-J., Rodilla, H., Friedman, R., Zhaunerchyk, V., Bourenkov, G., Schneider, T., Stake, J. & Katona, G. (2019) Clustering of atomic displacement parameters in bovine trypsin reveals a distributed lattice of atoms with shared chemical properties. Scientific reports, 9, 19281.

  Ahlberg Gagner, V., Jensen, M., & Katona, G. (2021) Estimating the probability of coincidental similarity between atomic displacement parameters with machine learning Machine Learning: Science and Technology, 2, 035033.

• Machine learning from biophysical experiments
  
• With increasing amount of biophysical data it is often difficult for a human to identify patterns and provide explanations for experimental observations. This is partly due to the sheer amount of data, but also the interactions between the model components of large systems is difficult to comprehend with a human brain. Although making predictions with advanced models have an important diagnostic value, we do not stop with sucessful predictions. We use black-box classification tools and prediction engines only for evaluating the usefulness of features and detecting the existence of patterns, but we aim to develop interpretable models, often based on Bayesian principles. Application areas include, but not limited to X-ray crystallography, structure analysis, progress curve analysis in thermophoresis and reaction kinetics and pattern detection in peptid binding.

  
  
  

  References:

  Katona, G., Garcia-Bonete, M.-J. & Lundholm, I.V. (2016) Estimating the difference between structure-factor amplitudes using multivariate Bayesian inference. Acta cryst. Section A, 72(3), 406-11.

  Sharma, A., Johansson, L., Dunevall, E., Wahlgren, W.Y., Neutze, R. & Katona, G. (2017) Asymmetry in serial femtosecond crystallography data. Acta cryst. Section A, 73(2), 93-101.

  Ahlberg Gagner, V., Jensen, M., & Katona, G. (2021) Estimating the probability of coincidental similarity between atomic displacement parameters with machine learning Machine Learning: Science and Technology, 2, 035033.

  Garcia-Bonete, M.-J., Jensen, M., Recktenwald, C. V., Rocha, S., Stadler, V., Bokarewa, M. & Katona, G. (2017) Bayesian Analysis of MicroScale Thermophoresis Data to Quantify Affinity of Protein: Protein Interactions with Human Survivin. Scientific reports, 7(1), 16816.

  Garcia-Bonete, M.-J. & Katona, G. (2019) Bayesian machine learning improves single-wavelength anomalous diffraction phasing. Acta cryst. Section A., 75, 851-60.

  Gagner, V. A., Lundholm, I., Garcia-Bonete, M.-J., Rodilla, H., Friedman, R., Zhaunerchyk, V., Bourenkov, G., Schneider, T., Stake, J. & Katona, G. (2019) Clustering of atomic displacement parameters in bovine trypsin reveals a distributed lattice of atoms with shared chemical properties. Scientific reports, 9, 19281.

• Photosynthesis
  
• Photosynthesis is the main source of energy in the biosphere. Our research focuses on how light is captured by proteins embedded in membrane bilayers. Through a multidisciplinary approach we detect dynamical events in these proteins which assist the conversion of light energy to chemical energy. Our studies mainly focus on the photosynthetic apparatus of purple bacteria, but in addition we study the conformational changes occuring in bacteriorhodopsin, a light driven proton pump. We are also interested in the machinery of higher plants that allows nuclear proteins to be transported into the chloroplast.

  References:

  Dods, R., Bath, P., Morozov, D., Gagner, V. A., Arnlund, D., Luk, H. L., Kubel, J., Maj, M., Vallejos, A., Wickstrand, C., Bosman, R., Beyerlein, K. R., Nelson, G., Liang, M., Milathianaki, D., Robinson, J., Harimoorthy, R., Berntsen, P., Malmerberg, E., Johansson, L., Andersson, R., Carbajo, S., Claesson, E., Conrad, C. E., Dahl, P., Hammarin, G., Hunter, M. S., Li, C., Lisova, S., Royant, A., Safari, C., Sharma, A., Williams, G. J., Yefanov, O., Westenhoff, S., Davidsson, J., DePonte, D. P., Boutet, S., Barty, A., Katona, G., Groenhof, G., Branden, G. & Neutze, R. (2020) Ultrafast structural changes within a photosynthetic reaction centre. Nature, 589(7841), 310-14.

  Wohri, A. B.; Katona, G.; Johansson, L. C.; Fritz, E.; Malmerberg, E.; Andersson, M.; Vincent, J.; Eklund, M.; Cammarata, M.; Wulff, M.; Davidsson, J.; Groenhof, G.; Neutze, R. (2010) Light-Induced Structural Changes in a Photosynthetic Reaction Center Caught by Laue Diffraction Science, 328, 630-633.

  Wohri, A. B., Wahlgren W. Y., Malmerberg, E., Johansson, L.C., Neutze, R. & Katona, G. (2009) Lipidic sponge phase crystal structure of a photosynthetic reaction center reveals peripheral lipids. Biochemistry 48(41), 9831-8.

  Katona, G., Andreasson, U., Gourdon, P., Snijder, A., Hansson, O., Andreasson, L.-E. & Neutze, R. (2005) Conformational regulation of charge recombination reactions in a photosynthetic bacterial reaction center. Nat. Struct. and Mol. Biol. 12(7), 630-1.

• Serine proteases
  
• Proteases are ubiquitous in prokaryotes and eukaryotes and serve important and diverse biological functions. These include central biological processes like fibrinolysis, hemostasis, complement reaction, and the digestion of dietary proteins.  The active site serine proteases consist of a catalytic triad formed by a serine, a histidine and an aspartate residue. We are both interested in the enzyme mechanism of serine proteases and the different roles they play in an organism.  We trapped elastase in a covalently linked acyl-enzyme state and solved the X-ray structure at 0.95 A resolution. Comparison to other ultra-high resolution structures revealed the subtle conformational changes associated with the acyl-enzyme state. Canonical inhibitors are also provide useful analogy to the initial Michaelis complex prior acylation. A 1.2 A resolution structure made it possible to study the shortening of hydrogen bonds between the substrate and enzyme along the reaction pathway: a mechanism, which links together catalytic efficiency and substrate binding. More recently at even higher resolution in a Michaelis complex (0.93 A) we observed a new protonation state for the serine protease active site, which could be possibly relevant at the physiological pH of the intestine.
  

  References:

  Wahlgren, W.Y., Pál, G., Kardos, J., Porrogi, P., Szenthe, B., Patthy, A., Gráf, L. & Katona, G. (2011) The catalytic aspartate is protonated in the Michaelis complex formed between trypsin and an in vitro evolved substrate-like inhibitor: a refined mechanism of serine protease action. J. Biol. Chem., 286(5), 3587-96.
  
  Fodor, K., Harmat, V., Neutze, R., Szilagyi, L. Graf, L. & Katona, G. (2006) Enzyme:substrate hydrogen bond shortening during the acylation phase of serine protease catalysis. Biochemistry 45(7), 2114-21.
  
  Katona, G., Wilmouth, R. C., Wright, P. A., Berglund, G. I., Hajdu, J., Neutze, R. & Schofield, C. J. (2002) X-ray structure of a serine protease acyl-enzyme complex at 0.95 A resolution. J. Biol. Chem.277(24), 21962-21970.
  
  Gagner, V. A., Lundholm, I., Garcia-Bonete, M.-J., Rodilla, H., Friedman, R., Zhaunerchyk, V., Bourenkov, G., Schneider, T., Stake, J. & Katona, G. (2019) Clustering of atomic displacement parameters in bovine trypsin reveals a distributed lattice of atoms with shared chemical properties. Scientific reports, 9, 19281.
  
  Jensen, M., Ahlberg Gagner, V., Cabello Sanchez, J., Bengtsson, A. U. J., Ekstrom, J. C., Bjorg Ulfarsdottir, T., Garcia-Bonete, M.-J., Jurgilaitis, A., Kroon, D., Pham, V. T., Checcia, S., Coudert-Alteirac, H., Schewa, S., Rossle, M., Rodilla, H., Stake, J., Zhaunerchyk, V., Larsson, J. & Katona, G. (2021) High-resolution macromolecular crystallography at the FemtoMAX beamline with time-over-threshold photon detection. J. Synchrotron Radiat., 28(1), 64-70.
  
• Protein-protein interactions
  

• We are studying the structural aspects of protein:protein interactions with X-ray crystallography and small/wide angle X-ray scattering techniques. Motor proteins are responsible for cellular movements and transporting cellular components within the cell. They frequently self assemble or associate to other proteins in order to perform their functions. For example the protein metastazin (S100A4) disrupts the formation of filaments of myosin 2 isoforms . Metastazin gets activated by calcium ions which enables it to bind to the tail piece of myosin 2. This leads to the dissociation of filaments and the increased cytoskeletal dynamics and mobility, which is frequently observed in tumor cells capable forming metastases. We described the interaction using the crystal structure of S100A4–nonmuscle myosin 2A tail fragment complex. Surprisingly the structure revealed that only a single chain of myosin 2 binds to a homodimer of metastazin. The binding of the asymmetric myosin 2 to initially symmetric metastazin causes conformational differences in the two subunit of metastazin and presumably increases the dynamics of the ternary complex.
  

  
  

  References:

  Kiss, B., Duelli, A., Radnai, L., Kekesi, A. K., Katona, G. & Nyitray, L. (2012) Crystal structure of the S100A4–nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism. PNAS, 109(16),6048-53.
  
  Rapali, P., Radnai, L., Süveges, D., Harmat, V., Tölgyesi, F., Wahlgren, W.Y., Katona, G., Nyitray, L. & Pál, G. (2011) Directed Evolution Reveals the Binding Motif Preference of the LC8/DYNLL Hub Protein and Predicts Large Numbers of Novel Binders in the Human Proteome. PloS One, 6(4), e18818.