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Laboratory of Structural Biology of Signaling Proteins

Laboratory of Structural Biology of Signaling Proteins

Our Laboratory is focused on structural biology (the relationship between the structure and function of certain groups of proteins), particularly we focus on the proteins which participate in the signal transmission in the cell. Among methods we use are recombinant protein expression, biophysical characterization, study of intermolecular interactions, protein structure and interaction surfaces. All these methods enable us to better understand the details how the activity and function of protein-protein complexes is regulated. Our research is focused mainly on:

  • Structural biology of 14-3-3 proteins and their complexes
  • Mechanism of regulation of proteinkisases CaMKK1, CaMKK2 and ASK1
  • Study of inhibition of protease caspase-2 and ligase Nedd4-2 by 14-3-3 protein
  • Study of DNA-binding domain of transcription factor FOXO4

EXTERNAL WEBSITE OF THE LABORATORY

Projects

Achievements

NEW FINDINGS ON THE STRUCTURE OF THE FOXO4: p53 COMPLEX - A KEY FACTOR IN SENESCENCE REGULATION (9.4.2022)

NEW FINDINGS ON THE STRUCTURE OF THE FOXO4: p53 COMPLEX - A KEY FACTOR IN SENESCENCE REGULATION (9.4.2022)

Transcription factor p53 protects cells against tumorigenesis when subjected to various cellular stresses. Under stress conditions, p53 interacts with another transcription factor, FOXO4 (Forkhead box O 4), and together they increase the production of p21 protein, which triggers the process of cell aging (senescence). However, the molecular mechanism of upregulation of p21 transcription is still unclear. In a work published in the Protein Science journal, scientific teams of Dr. Obsilova (IPHYS CAS), prof. Obsil (Faculty of Science, Charles University and IPHYS CAS) and their colleagues from IOCB CAS characterized interactions between p53 and FOXO4 at the molecular level. New knowledge about the structure of the complex may enable the development of specific inhibitors of the interaction between these two proteins, and subsequently in the development of new drugs aimed at the selective elimination of senescent cells.   More
Our new articles in Communications Biology

Our new articles in Communications Biology

Two accepted papers in Communications Biology: July and August 2021 Pavel Pohl, Rohit Joshi, Olivia Petrvalska, Tomas Obsil and Veronika Obsilova 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains | Communications Biology (nature.com) Commun. Biol. 2021 July 22; 4(1):899. Matej Horvath, Olivia Petrvalska, Petr Herman, Tomas Obsil and Veronika Obsilova 14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites | Communications Biology (nature.com) Commun. Biol. 2021 August 19; 4(1):986. IF = 6.268 More

Tomáš Obšil was awarded the title of professor

Prof. RNDr. Tomáš Obšil, Ph.D. was awarded by the title of professor at The Faculty of Science, Charles University, majoring in Physical Chemistry. Professors graduation will take place December 18, 2014. More

Publications

Mandal; R. - Kohoutová; Klára - Petrvalská; Olivia - Horváth; M. - Srb; Pavel - Veverka; Václav - Obšilová; Veronika - Obšil; Tomáš . FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA . Protein Science. 2022; 31(5)); e4287 . IF = 6.993 [ASEP] [ doi ]
Joshi; Rohit - Pohl; Pavel - Strachotová; D. - Herman; P. - Obšil; Tomáš - Obšilová; Veronika . Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains . Biophysical Journal. 2022; 121(7); 1299-1311 . IF = 3.699 [ASEP] [ doi ]
Pohl; Pavel - Joshi; Rohit - Petrvalská; Olivia - Obšil; Tomáš - Obšilová; Veronika . 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains . Communications Biology. 2021; 4(1)); 899 . IF = 6.548 [ASEP] [ doi ]
Obšilová; Veronika - Honzejková; K. - Obšil; Tomáš . Structural Insights Support Targeting ASK1 Kinase for Therapeutic Interventions . International Journal of Molecular Sciences. 2021; 22(24)); 13395 . IF = 6.208 [ASEP] [ doi ]
Neves; J. F. - Petrvalská; Olivia - Bosica; F. - Cantrelle; F. X. - Merzougui; H. - O'Mahony; G. - Hanoulle; X. - Obšil; Tomáš - Landrieu; I. Phosphorylated full-length Tau interacts with 14-3-3 proteins via two short phosphorylated sequences; each occupying a binding groove of 14-3-3 dimer . FEBS Journal. 2021; 288(6); 1918-1934 . IF = 5.622 [ASEP] [ doi ]
Košek; Dalibor - Grabundzija; I. - Lei; H. - Bilic; I. - Wang; H. - Jin; Y. - Peaslee; G. F. - Hickman; A. B. - Dyda; F. The large bat Helitron DNA transposase forms a compact monomeric assembly that buries and protects its covalently bound 5 '-transposon end . Molecular Cell. 2021; 81(20); 4271-4286.e4 . IF = 19.328 [ASEP] [ doi ]
Horváth; Matej - Petrvalská; Olivia - Herman; P. - Obšilová; Veronika - Obšil; Tomáš . 14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites . Communications Biology. 2021; 4(1)); 986 . IF = 6.548 [ASEP] [ doi ]
Boušová; Kristýna - Bednárová; Lucie - Zouharová; Monika - Vetýšková; Veronika - Poštulková; Klára - Hofbauerová; Kateřina - Petrvalská; Olivia - Vaněk; O. - Tripsianes; K. - Vondrášek; Jiří . The order of PDZ3 and TrpCage in fusion chimeras determines their properties—a biophysical characterization . Protein Science. 2021; 30(8); 1653-1666 . IF = 6.993 [ASEP] [ doi ]
Santo Lentini; D. - Petrvalská; Olivia - Obšilová; Veronika - Ottmann; Ch. - Obšil; Tomáš . Stabilization of Protein-Protein Interactions between CaMKK2 and 14-3-3 by Fusicoccins . ACS Chemical Biology. 2020; 15(11); 3060-3071 . IF = 5.100 [ASEP] [ doi ]
Pšenáková; Katarína - Hexnerová; Rozálie - Srb; Pavel - Obšilová; Veronika - Veverka; Václav - Obšil; Tomáš . The redox-active site of thioredoxin is directly involved in apoptosis signal-regulating kinase 1 binding that is modulated by oxidative stress . FEBS Journal. 2020; 287(8); 1626); 1644 . IF = 5.542 [ASEP] [ doi ]
Obšilová; Veronika - Obšil; Tomáš . The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases . International Journal of Molecular Sciences. 2020; 21(22)); 8824 . IF = 5.923 [ASEP] [ doi ]
Obšilová; Veronika - Obšil; Tomáš . A new role for 14-3-3 protein in steroidogenesis . FEBS Journal. 2020; 287(18); 3921-3924 . IF = 5.542 [ASEP] [ doi ]
Kalábová; Dana - Filandr; František - Alblová; Miroslava - Petrvalská; Olivia - Horváth; Matej - Man; Petr - Obšil; Tomáš - Obšilová; Veronika . 14-3-3 protein binding blocks the dimerization interface of caspase-2 . FEBS Journal. 2020; 287(16); 3494-3510 . IF = 5.542 [ASEP] [ doi ]
Valenti; D. - Neves; J. F. - Cantrelle; F. X. - Hristeva; S. - Santo Lentini; D. - Obšil; Tomáš - Hanoulle; X. - Levy; L. M. - Tzalis; D. - Landrieu; I. - Ottmann; Ch. Set-up and screening of a fragment library targeting the 14-3-3 protein interface . MedChemComm. 2019; 10(10); 1796-1802 . IF = 2.807 [ASEP] [ doi ]
Šmídová; Aneta - Staňková; Kateřina - Petrvalská; Olivia - Lazar; Josef - Sychrová; Hana - Obšil; Tomáš - Zimmermannová; Olga - Obšilová; Veronika . The activity of Saccharomyces cerevisiae Na+; K+/H+ antiporter Nha1 is negatively regulated by 14-3-3 protein binding at serine 481 . Biochimica Et Biophysica Acta-Molecular Cell Research. 2019; 1866(12)); 118534 . IF = 4.105 [ASEP] [ doi ]

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People

 RNDr. Veronika Obšilová, Ph.D.
 Head of the Laboratory
Prof. RNDr. Tomáš Obšil, Ph.D.
Deputy Head of the Laboratory (part time)

MgrDalibor Košek, Ph.D.
Junior Researcher
Mgr. Pavel Pohl
PhD Student
M.Sc. Rohit Ashok Joshi
PhD Student
M.Sc. Maša Janošev
PhD Student

Bc. Andrej Tekel

ext. - Undergraduate Student

Bc. Zuzana Janáčková
ext. - Undergraduate Student

Bc. Adam Brzezina

ext. - Undergraduate Student

Bc. Matúš Friček
ext.- Undergraduate Student
Mgr. Dana Kalábová
Technician
Bc. Gabriela Kočárová
Technician