Laboratory of Structural Biology of Transcription Regulation
We use the means of integrative structural biology for detailed understanding of various biological processes. We focus on validation of biomolecular interactions that play important roles in human pathologies and can be exploited for therapeutic intervention. In a joint effort with medicinal chemists we develop small molecule inhibitors for these interactions. We study protein interaction networks that are implicated in regulation of gene transcription and also contribute to development of haematological malignancies. One of them is the iteractome of an epigenetic reader LEDGF/p75 that tethers other factors to the actively transcribed genes on chromatin. Its activity is essential for development of the two distinct diseases: HIV infection and Mixed-lineage leukemia (MLL).
Lisa-Maria Weinhold 💬 firstname.lastname@example.org
Project: Structural relationship between subunits of chromatin remodeling complexes (since 2019)
Terézia Paulovčáková 💬 email@example.com
Project: Transient nuclear protein-protein interaction networks (since 2022)
Alexandra Gredová 💬 firstname.lastname@example.org
Project: Protein complexes in nucleosomal context (since 2023)
Magdalena Havlová (UCT Prague)
Lukáš Vrzal (UCT Prague), Ph.D.
Rozálie Hexnerová, Ph.D.
Markéta Hašplová (UCT Prague), Ing.
Matúš Drexler (UCT Prague), Ing.
Karolína Naušová, Mgr.
Lenka Vaneková, Ph.D.
Eliška Koutná, Ph.D.
Practical Course in Structural Biology (MC250P76)
Structural Biology of the Cell (MB151P117)
Drug Design (MB191P98)
Determination of the 3D structure of macromolecules (MC250P17)
Advanced NMR methods (MC270P08A)
Koutná, E. et al. Multivalency of nucleosome recognition by LEDGF. Nucleic Acids Res 24:gkad674 (2023).
Čermáková, K., Demeulemeester, J., Lux, V., et al. A ubiquitous disordered protein interaction module orchestrates transcription elongation. Science 374, 1113-1121 (2021).
Lux, V. et al. Molecular Mechanism of LEDGF/p75 Dimerization. Structure 28, 1288-1299 (2020).
Sharma, S. et al. Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation. Proc Natl Acad Sci U S A 115, E7053-E7062 (2018).
Hodges, H.C. et al. Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers. Nat Struct Mol Biol 25, 61-72 (2018).
Hnízda, A. et al. Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation. Leukemia 32, 1393-1403 (2018).
Hnízda, A. et al. Oligomeric interface modulation causes misregulation of purine 5 -nucleotidase in relapsed leukemia. BMC Biol 14, 91 (2016).
Těšina, P. et al. Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif. Nat Commun 6, 7968 (2015).
Čermáková, K. et al. Validation and structural characterization of the LEDGF/p75-MLL interface as a new target for the treatment of MLL-dependent leukemia. Cancer Res 74, 5139-51 (2014).