Biophysical Chemistry of Protein Complexes

Tomáš Obšil group

Biophysical Chemistry of Protein Complexes

Tomáš Obšil group

We study molecular mechanisms by which protein function can be regulated. In particular, we are interested in 14-3-3 proteins and their complexes with proteins involved in apoptosis, cancer, G-protein and calcium-triggered signaling pathways. We employ both biophysical (fluorescence spectroscopy, analytical ultracentrifugation, SAXS, mass spectrometry, X-ray crystallography, NMR, protein structure modeling, etc.) and biochemical (recombinant protein expression, site-directed mutagenesis) approaches to understand the details of how the activity and function of protein-protein complexes are regulated.

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People of the Group

Tomáš Obšil

Prof. RNDr., Ph.D.

Vice-head of the department, Professor

Klára Kohoutová

Mgr.

Doctoral student

Andrej Tekel

Mgr.

Doctoral student

Adam Brzezina

Mgr.

Doctoral student

Martin Hýbl

Bc.

Master student

Research Topics

FOXO-DBD

FOXO transcription factors control apoptosis, stress resistance and longevity in mammalian cells. Although the members of the FOXO family act as tumor suppressors in some cell types, emerging evidence suggests ...

Protein kinase ASK1

Protein kinase ASK1, a member of the mitogen-activated protein kinase kinase kinase family, activates JNK and p38 MAP kinase signaling pathways in response to various stress stimuli, including oxidative stress ...

Neutral trehalase Nth1

Neutral trehalase 1 (Nth1) catalyses the hydrolysis of trehalose to glucose. Trehalose is found in many organisms ranging from bacteria to higher plants, and in yeast it functions as a ...

Phosducin (Pdc)

Phosducin (Pdc) is a highly conserved acidic phosphoprotein that regulates visual signal transduction by modulating the
amount of transducin G_tαβγ heterotrimer through competition with the G_ta ...

14-3-3 proteins

14-3-3 proteins are a family of regulatory molecules, which specifically bind to phosphoserine (or phosphothreonine)- containing motifs (pSer/pThr) in a sequence-specific manner. Through these binding interactions, 14-3-3 proteins play ...

Selected Publications

P. Mystek V. Singh M. Horváth K. Honzejková P. Riegerová H. Evci M. Hof T. Obšil et al.
The minimal membrane requirements for BAX-induced pore opening upon exposure to oxidative stress

Biophysical Journal, 2024

V. Obsilova, and T. Obsil,
Look for the Scaffold: Multifaceted Regulation of Enzyme Activity by 14-3-3 Proteins

Physiol Res, 2024

V. Obsilova, and T. Obsil,
The yeast 14-3-3 proteins Bmh1 and Bmh2 regulate key signaling pathways

Frontiers in Molecular Biosciences, 11, 2024

K. Honzejkova, D. Kosek, V. Obsilova, and T. Obsil,
The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1

eLife, 13, 2024

B. A. Somsen E. Sijbesma S. Leysen K. Honzejkova E. J. Visser P. J. Cossar T. Obsil L. Brunsveld et al.
Molecular basis and dual ligand regulation of tetrameric estrogen receptor α/14-3-3ζ protein complex

Journal of Biological Chemistry, 299(7), 2023

nuclear receptors protein–protein interactions estrogen receptor 14-3-3 protein ppi stabilization

V. Obsilova, and T. Obsil,
Structural insights into the functional roles of 14-3-3 proteins

Frontiers in Molecular Biosciences, 9, 2022

K. Kohoutova V. Docekal M. J. Ausserlechner N. Kaiser A. Tekel R. Mandal M. Horvath V. Obsilova et al.
Lengthening the Guanidine–Aryl Linker of Phenylpyrimidinylguanidines Increases Their Potency as Inhibitors of FOXO3-Induced Gene Transcription

ACS Omega, 7(38), 2022

R. Mandal, K. Kohoutova, O. Petrvalska, M. Horvath, P. Srb, V. Veverka, V. Obsilova, and T. Obsil,
FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA

Protein Science, 31(5), 2022

R. Joshi, P. Pohl, D. Strachotova, P. Herman, T. Obsil, and V. Obsilova,
Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains

Biophysical Journal, 121(7), 2022

M. Horvath, O. Petrvalska, P. Herman, V. Obsilova, and T. Obsil,
14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites

Communications Biology, 4(986), 2021

V. Obsilova, K. Honzejkova, and T. Obsil,
Structural Insights Support Targeting ASK1 Kinase for Therapeutic Interventions

International Journal of Molecular Sciences, 22(24), 2021

S. Leysen R. J. Burnley E. Rodriguez L.-G. Milroy L. Soini C. J. Adamski L. Nitschke R. Davis et al.
A Structural Study of the Cytoplasmic Chaperone Effect of 14-3-3 Proteins on Ataxin-1

Journal of Molecular Biology, 433(19), 2021

Neves J.F. Petrvalská O. Bosica F. Cantrelle F.-X. et al.
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, 288, 1918-1934, 2021

P. Pohl, R. Joshi, O. Petrvalska, T. Obsil, and Obsilova V,
14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains

Commun. Biol., 2021

D. Kalabova, F. Filandr, M. Alblova, O. Petrvalska, M. Horvath, P. Man, T. Obsil, and V. Obsilova,
14-3-3 protein binding blocks the dimerization interface of caspase-2

The FEBS Journal, 287(16), 2020

M. Wolter, D. L. Santo, P. Herman, A. Ballone, F. Centorrino, T. Obsil, and C. Ottmann,
Interaction of an IpkappaBpalpha Peptide with 14-3-3

ACS Omega, 5(10), 2020

D. L. Santo, O. Petrvalska, V. Obsilova, C. Ottmann, and T. Obsil,
Stabilization of Protein\textendashProtein Interactions between CaMKK2 and 14\textendash3\textendash3 by Fusicoccins

ACS Chemical Biology, 15(11), 2020

V. Obsilova, and T. Obsil,
The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases

International Journal of Molecular Sciences, 21(22), 2020

K. Psenakova, R. Hexnerova, P. Srb, V. Obsilova, V. Veverka, and T. Obsil,
The redox-active site of thioredoxin is directly involved in apoptosis signal-regulating kinase 1 binding that is modulated by oxidative stress

The FEBS Journal, 287(8), 2019

J. Hagenbuchner V. Obsilova T. Kaserer N. Kaiser B. Rass K. Psenakova V. Docekal M. Alblova et al.
Modulating FOXO3 transcriptional activity by small, DBD-binding molecules

eLife, 8, e48876, 2020

D. Valenti J. F. Neves F.-X. Cantrelle S. Hristeva D. L. Santo T. Obšil X. Hanoulle L. M. Levy et al.
Set-up and screening of a fragment library targeting the 14-3-3 protein interface

Med. Chem. Commun., 10, 1796-1802, 2019

M. Alblova, A. Smidova, D. Kalabova, D. L. Santo, T. Obsil, and V. Obsilova,
Allosteric activation of yeast enzyme neutral trehalase by calcium and 14-3-3 protein

Physiol. Res., 68(2), 147-160, 2019

K. Psenakova, K. Kohoutova, V. Obsilova, M. J. Ausserlechner, V. Veverka, and T. Obsil,
Forkhead Domains of FOXO Transcription Factors Differ in both Overall Conformation and Dynamics

Cells, 8(8), 966, 2019

A. Smidova, K. Stankova, O. Petrvalska, J. Lazar, H. Sychrova, T. Obsil, O. Zimmermannova, and V. Obsilova,
The activity of Saccharomyces cerevisiae Na\mathplus, K\mathplus/H\mathplus antiporter Nha1 is negatively regulated by 14-3-3 protein binding at serine 481

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1866(12), 2019

A. Smidova, M. Alblova, D. Kalabova, K. Psenakova, M. Rosulek, P. Herman, T. Obsil, and V. Obsilova,
14-3-3 protein masks the nuclear localization sequence of caspase-2

The FEBS Journal, 285(22), 2018

S. Kylarova, K. Psenakova, P. Herman, V. Obsilova, and T. Obsil,
CaMKK2 kinase domain interacts with the autoinhibitory region through the N-terminal lobe including the RP insert

Biochimica et Biophysica Acta (BBA) - General Subjects, 1862(10), 2018

K. Psenakova, O. Petrvalska, S. Kylarova, D. L. Santo, D. Kalabova, P. Herman, V. Obsilova, and T. Obsil,
14-3-3 protein directly interacts with the kinase domain of calcium/calmodulin-dependent protein kinase kinase (CaMKK2)

Biochimica et Biophysica Acta (BBA) - General Subjects, 1862(7), 2018