Změnit instituci
Pokročilé nano a mikrotechnologie Pokročilé materiály Strukturní biologie Gen. a prot. rostlin. systémů Molekulární medicína Výzkum mozku a lidské mysli Molekulární vet. medicína

Výzkumná skupina Lukáše Žídka

Vedoucí výzkumné skupiny
Researcher ID
Telefon: +420 54949 8393
E-mail: ,
Kancelář:
Zástupce vedoucího výzkumné skupiny
Researcher ID
Telefon: +420 54949 3847
E-mail:
Kancelář:

Research areas

  • Structure, dynamics and interactions of proteins
  • Intrinsically disordered proteins
  • Development and application of NMR methodology

Main objectives

  • Development of new methodologies for the investigation of biomolecular structures, interactions, and dynamics.
  • Investigations of the biomolecular structures and interactions and their relationship with physiological functions, diseases and therapies.
  • Production of pure and homogeneous proteins for the structural analysis.
  • Production of monoclonal antibodies, with emphasis on the quality of the antigen – antibody selection.  Selection of binding molecules from synthetic DNA libraries for diagnostic and therapeutic use.

Content of research

In collaboration with L. Krasný (Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic), we study subunits and sigma-factors unique for RNA polymerase of Gram-positive bacteria. We have determined structure of well-ordered N-terminal domain of delta subunit and characterized structural features of its intrinsically disordered C-terminal domain. In addition to the structural description, we characterized dynamics of both domains at various time scales using NMR relaxation. Investigation of other subunits and sigma-factors is in progress.

Multidisciplinary research of proteins involved in plant hormone signaling cascades is an example of a collaborative project within CEITEC (J. Hejtko, Functional Genomics and Proteomics of Plants). We have studied dynamics of receiver domain of the sensory kinase CKI1 and characterized its interactions with Mg(2+) ions and a phosphate analogue. We are involved in characterization of interactions of the CKI1 receiver domain with its down-stream partners and in structural studies of other sensory kinases (e.g. ETR1).

Traditionally, the strength of the group has been development of NMR methodology for atomic-resolution studies of proteins and nucleic acids. Recently, several fruitful collaborations witnessed that we are able to apply our know-how to solve real biological problems that were hard to attack by the conventional approaches. In the future, we would like to continue to develop in this direction and to complement the existing successful collaboration with our own projects. We plan to study dynamics, structural properties, function and regulation of Microtubule Associated Protein 2c (MAP2c), a cytoskeletal protein important for development of neuronal cells. The free form of the protein is disordered and relatively large (49 kDa), which makes it a challenging target for NMR. Our preliminary results show that the methodology developed in our group is sufficient for such a type of molecule.

Delta
  3D structure of the delta subunit of RNA polymerase from Bacillus subtilis including disordered C-terminal tail determined by NMR spectroscopy.

seznam / vizitky

Jméno a pozice

E-mail

Telefon

prof. Mgr. Lukáš Žídek, Ph.D.
Vedoucí výzkumné skupiny
+420 54949 8393
prof. RNDr. Vladimír Sklenář, DrSc.
Koordinátor výzkumných infrastruktur
+420 54949 7022
RNDr. Mgr. Jozef Hritz, Ph.D.
Výzkumný pracovník
+420 54949 3847
Mgr. Petr Padrta, Ph.D.
Výzkumný pracovník
+420 54949 6355
Mgr. Jana Pavlíková Přecechtělová, Ph.D.
Výzkumný pracovník
Dr. Tanvir Shaikh
Výzkumný pracovník
+420 54949 7577
RNDr. Mgr. Arnošt Mládek, Ph.D.
Výzkumný pracovník - postdok
+420 54949 5398
Mgr. Zuzana Gelová
PhD student
Mgr. Kateřina Hanáková
Odborná pracovnice - PhD studentka
+420 54949 8442
Ing. Dominika Ledvinová
Odborná pracovnice - PhD studentka
+420 54949 8442
Mgr. Zuzana Jaseňáková
PhD student
+420 54949 2615
Mgr. Vojtěch Kubáň
PhD student
Mgr. Kateřina Melková
PhD student
+420 54949 2523
Mgr. Milan Zachrdla
PhD student
+420 54949 2523
Mgr. Vojtěch Zapletal
PhD student
+420 54949 8147, +420 54949 2523
Mgr. Šimon Džatko
Student
+420 54949 7832
Mgr. Martin Gajarský
Student
+420 54949 7832
Mgr. Michaela Krafčíková
Student
+420 54949 7832
Mgr. Olga Otrusinová
PhD student
+420 54949 2615
Mgr. Zuzana Trošanová
Mgr. Petr Louša
Student
Séverine Jansen, PhD.
Výzkumný pracovník
+420 54949 2615
RNDr. Hana Konečná
Odborná pracovnice
+420 54949 5050
Bc. Tereza Chmelíková
Student
Mgr. Michaela Markvartová
Bc. Hana Štégnerová
Vladimír Jonas
Sudhir Kumar Pal
Mgr. Jakub Šebera, Ph.D.
Mgr. Pavlína Víšková
Student
Bc. Hana Zigová
Student
Mgr. Daniel Krafčík
Student
Norbert Gašparik

VYBRANÉ PUBLIKACE

2017

  • GROCHALOVA, M; KONECNA, H; STEJSKAL, K; POTESIL, D; FRIDRICHOVA, D; SRBOVA, E; ORNEROVA, K; ZDRAHAL, Z, 2017:Deep coverage of the beer proteome. JOURNAL OF PROTEOMICS 162 , p. 119 - 124.
  • JANSEN, S; MELKOVA, K; TROSANOVA, Z; HANAKOVA, K; ZACHRDLA, M; NOVACEK, J; ZUPA, E; ZDRAHAL, Z; HRITZ, J; ZIDEK, L, 2017:Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3 zeta-binding sites reveals key differences between MAP2c and its homolog Tau. JOURNAL OF BIOLOGICAL CHEMISTRY 292 (16), p. 6715 - 6727.
  • LINKE, F; HARENBERG, M; NIETERT, M M; ZAUNIG, S; VON BONIN, F; ARLT, A; SZCZEPANOWSKI, M; WEICH, H A; LUTZ S; DULLIN, C; JANOVSKÁ, P; KRAFČÍKOVÁ, M; TRANTÍREK, L; OVESNÁ, P; KLAPPER, W; BEISSBARTH, T; ALVES, F; BRYJA, V; TRÜMPER, L; WILTING, J, KUBE, D, 2017:Microenvironmental interactions between endothelial and lymphoma cells: a role for the canonical WNT pathway in Hodgkin lymphoma. Leukemia 31 (2), p. 361 - 372.
  • LOUSA, P; NEDOZRALOVA, H; ZUPA, E; NOVACEK, J; HRITZ, J, 2017:Phosphorylation of the regulatory domain of human tyrosine hydroxylase 1 monitored using non-uniformly sampled NMR. BIOPHYSICAL CHEMISTRY 223 , p. 25 - 29.
  • MAJERSKA, J; SCHRUMPFOVA, PP; DOKLADAL, L; SCHOROVA, S; STEJSKAL, K; OBORIL, M; HONYS, D; KOZAKOVA, L; POLANSKA, PS; SYKOROVA, E, 2017:Tandem affinity purification of AtTERT reveals putative interaction partners of plant telomerase in vivo. PROTOPLASMA 254 (4), p. 1547 - 1562.
  • NAGY, G; OOSTENBRINK, C; HRITZ, J, 2017:Exploring the binding pathways of the 14-3-3ζ protein: Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints. PLoS ONE 7 (12)

2016

  • CERVENKA, I; VALNOHOVA, J; BERNATIK, O; HARNOS, J; RADSETOULAL, M; SEDOVA, K; HANAKOVA, K; POTESIL, D; SEDLACKOVA, M; SALASOVA, A; STEINHART, Z; ANGERS, S; SCHULTE, G; HAMPL, A; ZDRAHAL, Z; BRYJA, V, 2016:Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113 (33), p. 9304 - 9309.
  • PEKAROVA, B; SZMITKOWSKA, A; DOPITOVA, R; DEGTJARIK, O; ZIDEK, L; HEJATKO, J, 2016:Structural Aspects of Multistep Phosphorelay-Mediated Signaling in Plants. MOLECULAR PLANT 9 (1), p. 71 - 85.
  • RUBIO-MARRERO, EN; VINCELLI, G; JEFFRIES, CM; SHAIKH, TR; PAKOS, IS; RANAIVOSON, FM; VON DAAKE, S; DEMELER, B; DE JACO, A; PERKINS, G; ELLISMAN, MH; TREWHELLA, J; COMOLETTI, D, 2016:Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1. JOURNAL OF BIOLOGICAL CHEMISTRY 291 (11), p. 5788 - 5802.
  • SHASMAL, M; DEY, S; SHAIKH, TR; BHAKTA, S; SENGUPTA, J, 2016:E. coli metabolic protein aldehyde-alcohol dehydrogenase-E binds to the ribosome: a unique moonlighting action revealed. SCIENTIFIC REPORTS 6
  • SLANINOVA, V; KRAFCIKOVA, M; PEREZ-GOMEZ, R; STEFFAL, P; TRANTIREK, L; BRAY, SJ; KREJCI, A, 2016:Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle. OPEN BIOLOGY 6 (2)
  • VAVRINSKA, A; ZELINKA, J; SEBERA, J; SYCHROVSKY, V; FIALA, R; BOELENS, R; SKLENAR, V; TRANTIREK, L, 2016:Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions (vol 64, pg 53, 2016). JOURNAL OF BIOMOLECULAR NMR 65 (1), p. 49 - 49.
  • VAVRINSKA, A; ZELINKA, J; SEBERA, J; SYCHROVSKY, V; FIALA, R; BOELENS, R; SKLENAR, V; TRANTIREK, L, 2016:Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions. JOURNAL OF BIOMOLECULAR NMR 64 (1), p. 53 - 62.

2015

  • KOZAKOVA, L; VONDROVA, L; STEJSKAL, K; CHARALABOUS, P; KOLESAR, P; LEHMANN, AR; ULDRIJAN, S; SANDERSON, CM; ZDRAHAL, Z; PALECEK, JJ, 2015:The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex. CELL CYCLE 14 (6), p. 920 - 930.
  • ZDARSKA, M; DOBISOVA, T; GELOVA, Z; PERNISOVA, M; DABRAVOLSKI, S; HEJATKO, J, 2015:Illuminating light, cytokinin, and ethylene signalling crosstalk in plant development. JOURNAL OF EXPERIMENTAL BOTANY 66 (16), p. 4913 - 4931.

2014

  • BERNATIK, O; SEDOVA, K; SCHILLE, C; GANJI, RS; CERVENKA, I; TRANTIREK, L; SCHAMBONY, A; ZDRAHAL, Z; BRYJA, V, 2014:Functional Analysis of Dishevelled-3 Phosphorylation Identifies Distinct Mechanisms Driven by Casein Kinase 1 epsilon and Frizzled5. JOURNAL OF BIOLOGICAL CHEMISTRY 289 (34), p. 23520 - 23533.
  • BORKOVCOVA, P; PEKAROVA, B; VALKOVA, M; DOPITOVA, R; BRZOBOHATY, B; JANDA, L; HEJATKO, J, 2014:Antibodies against CKI1(RD), a receiver domain of the sensor histidine kinase in Arabidopsis thaliana: From antigen preparation to in planta immunolocalization. PHYTOCHEMISTRY 100 , p. 6 - 15.
  • GARDNER, CL; HRITZ, J; SUN, CQ; VANLANDINGHAM, DL; SONG, TY; GHEDIN, E; HIGGS, S; KLIMSTRA, WB; RYMAN, KD, 2014:Deliberate Attenuation of Chikungunya Virus by Adaptation to Heparan Sulfate-Dependent Infectivity: A Model for Rational Arboviral Vaccine Design. PLOS NEGLECTED TROPICAL DISEASES 8 (2)
  • HRITZ, J; BYEON, IJL; KRZYSIAK, T; MARTINEZ, A; SKLENAR, V; GRONENBORN, AM, 2014:Dissection of Binding between a Phosphorylated Tyrosine Hydroxylase Peptide and 14-3-3 zeta: A Complex Story Elucidated by NMR. BIOPHYSICAL JOURNAL 107 (9), p. 2185 - 2194.
  • LUI, VWY; PEYSER, ND; NG, PKS; HRITZ, J; ZENG, Y; LU, YL; LI, H; WANG, L; GILBERT, BR; GENERAL, IJ; BAHAR, I; JU, ZL; WANG, ZH; PENDLETON, KP; XIAO, X; DU, Y; VRIES, JK; HAMMERMAN, PS; GARRAWAY, LA; MILLS, GB; JOHNSON, DE; GRANDIS, JR, 2014:Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111 (3), p. 1114 - 1119.
  • OBR, M; HADRAVOVA, R; DOLEZAL, M; KRIZOVA, I; PAPOUSKOV, V; ZIDEK, L; HRABAL, R; RUML, T; RUMLOVA, M, 2014:Stabilization of the beta-hairpin in Mason-Pfizer monkey virus capsid protein- a critical step for infectivity. RETROVIROLOGY 11
  • YURENKO, YP; NOVOTNY, J; MITORAJ, MP; SKLENAR, V; MICHALAK, A; MAREK, R, 2014:Nucleic Acid Quadruplexes Based on 8-Halo-9-deazaxanthines: Energetics and Noncovalent Interactions in Quadruplex Stems. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 10 (12), p. 5353 - 5365.
  • ZABRADY, M; HRDINOVA, V; MULLER, B; CONRAD, U; HEJATKO, J; JANDA, L, 2014:Targeted In Vivo Inhibition of Specific Protein-Protein Interactions Using Recombinant Antibodies. PLOS ONE 9 (10)

2013

  • HABA, NY; GROSS, R; NOVACEK, J; SHAKED, H; ZIDEK, L; BARDA-SAAD, M; CHILL, JH, 2013:NMR Determines Transient Structure and Dynamics in the Disordered C-Terminal Domain of WASp Interacting Protein. BIOPHYSICAL JOURNAL 105 (2), p. 481 - 493.
  • NOVACEK, J; JANDA, L; DOPITOVA, R; ZIDEK, L; SKLENAR, V, 2013:Efficient protocol for backbone and side-chain assignments of large, intrinsically disordered proteins: transient secondary structure analysis of 49.2 kDa microtubule associated protein 2c. JOURNAL OF BIOMOLECULAR NMR 56 (4), p. 291 - 301.
  • PAPOUSKOVA, V; KADERAVEK, P; OTRUSINOVA, O; RABATINOVA, A; SANDEROVA, H; NOVACEK, J; KRASNY, L; SKLENAR, V; ZIDEK, L, 2013:Structural Study of the Partially Disordered Full-Length delta Subunit of RNA Polymerase from Bacillus subtilis. CHEMBIOCHEM 14 (14), p. 1772 - 1779.
  • PAPOUSKOVA, V; NOVACEK, J; KADERAVEK, P; SANDEROVA, H; RABATINOVA, A; ZIDEK, L; KRASNY, L; SKLENAR, V, 2013:Structural study of partially disordered delta subunit of RNA polymerase unique for gram-positive bacteria. FEBS JOURNAL 280 , p. 146 - 147.

2012

  • FERUS, M; CIVIS, S; MLADEK, A; SPONER, J; JUHA, L; SPONER, JE, 2012:On the Road from Formamide Ices to Nucleobases: IR-Spectroscopic Observation of a Direct Reaction between Cyano Radicals and Formamide in a High-Energy Impact Event. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 (51), p. 20788 - 20796.
  • PAVLIKOVA, N; BLAHOVA, L; KLAN, P; BATHULA, SR; SKLENAR, V; GIESY, JP; BLAHA, L, 2012:Enantioselective effects of alpha-hexachlorocyclohexane (HCH) isomers on androgen receptor activity in vitro. CHEMOSPHERE 86 (1), p. 65 - 69.

2011

  • NOVACEK, J; ZAWADZKA-KAZIMIERCZUK, A; PAPOUSKOVA, V; ZIDEK, L; SANDEROVA, H; KRASNY, L; KOZMINSKI, W; SKLENAR, V, 2011:5D C-13-detected experiments for backbone assignment of unstructured proteins with a very low signal dispersion. JOURNAL OF BIOMOLECULAR NMR 50 (1), p. 1 - 11.
  • PEKAROVA, B; KLUMPLER, T; TRISKOVA, O; HORAK, J; JANSEN, S; DOPITOVA, R; BORKOVCOVA, P; PAPOUSKOVA, V; NEJEDLA, E; SKLENAR, V; MAREK, J; ZIDEK, L; HEJATKO, J; JANDA, L, 2011:Structure and binding specificity of the receiver domain of sensor histidine kinase CKI1 from Arabidopsis thaliana. PLANT JOURNAL 67 (5), p. 827 - 839.

2010

  • MOTACKOVA, V; SANDEROVA, H; ZIDEK, L; NOVACEK, J; PADRTA, P; SVENKOVA, A; KORELUSOVA, J; JONAK, J; KRASNY, L; SKLENAR, V, 2010:Solution structure of the N-terminal domain of Bacillus subtilis delta subunit of RNA polymerase and its classification based on structural homologs. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 78 (7), p. 1807 - 1810.
  • PRECECHTELOVA, J; NOVAK, P; MUNZAROVA, ML; KAUPP, M; SKLENAR, V, 2010:Phosphorus Chemical Shifts in a Nucleic Acid Backbone from Combined Molecular Dynamics and Density Functional Calculations. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 132 (48), p. 17139 - 17148.

2009

  • MACEK, P., CHMELIK, J., KRIZOVA, I., KADERAVEK, P., ZIDEK, L., WILDOVA, M., HADRAVOVA, R., CHALOUPKOVA, R., PICHOVA, I., RUML, T., RUMLOVA, M., SKLENAR, V., 2009:NMR structure of the N-terminal domain of capsid protein from the Mason-Pfizer monkey virus. Journal of Molecular Biology 392 (1), p. 100 - 114.
  • MATEJKOVA, M; ZIDKOVA, J; ZIDEK, L; WIMMEROVA, M; CHMELIK, J; SKLENAR, V, 2009:Investigation of Thermal Denaturation of Barley Nonspecific Lipid Transfer Protein 1 (ns-LTP1b) by Nuclear Magnetic Resonance and Differential Scanning Calorimetry. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 57 (18), p. 8444 - 8452.

GRANTY

  • Podjednotky určující DNA specificitu bakteriální RNA polymerázy s flexibilními doménami: funkce a dynamika (GA13-16842S), Czech Science Foundation - Standard Grants, 2013 - 2017
  • Určení struktury lidské 14-3-3zeta v komplexu s dvojitě fosforylovanou lidskou tyrosin hydroxylázou 1 (4SGA8679), South Moravian Region - SoMoPro, 2014 - 2016
  • Efektivní výpočty volných energií a konfiguračního vzorkování protein-proteinových interakcí (I 1999-N28), Czech Science Foundation - International Projects, 2015 - 2017
  • iNEXT - Infrastructure for NMR, EM and X-ray crystallography for translational research (653706), H2020 - Excellent science - Research Infrastructures, 2015 - 2019

1. Impact of 14-3-3 protein on the formation of protein aggregates involved in neurodegenerative diseases

Supervisor:  RNDr. Mgr. Jozef Hritz, Ph.D.
Consultant: doc. Mgr. Vítězslav Bryja, Ph.D., Mgr. Jan Přibyl, Ph.D.

Annotation:

The neuronal cells of patients suffering from neurodegenerative diseases are characteristic by possession of aggregates of several proteins such as tau and Abeta protein. They form toxic aggregates to the different extend depending on the environment and their state (e.g. different post-translational modifications or specific conformational state). The main aim of this PhD project will be to quantify the extent of aggregation of three selected proteins in vitro and in the cell environment. Dependence of aggregation on phosphorylation and the potential interaction with various forms of 14-3-3 proteins will be analyzed mostly by biophysical interaction techniques and the atomic force microscopy. The biological relevance of the in-vitro findings will be tested in cell cultures by fluorescence microscopy.

2. Structural changes of the selected protein fibrils induced by phosphorylation and the interaction with 14-3-3 proteins

Supervisor:  RNDr. Mgr. Jozef Hritz, Ph.D.
Consultant: doc. Mgr. Vítězslav Bryja, Ph.D., Dr. Tanvir Shaikh

Annotation:

Several neurodegenerative diseases are asociated with the formation of fibrous (fibrillar) protein agreggates. The fibrillization of amyloid beta peptide into amyloid plaques and the agregation of hyperphosphorylated tau protein into neurofibrillar tangles are main neuropatological signs of Alzheimer disease. Studying of how different factors influence the formation of protein fibrils is the key for understanding this neurodegerative processes. The main aim of this PhD project will be characterization of structural changes in the formation of protein fibrils due to different phosphorylation state and the interaction with 14-3-3 proteins. Interdisciplinary approach combining molecular biology and structural biology (mainly cryoEM tomography) methods will be applied. Molecular binding mode involving 14-3-3 will be elucidated by NMR.

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