Laboratory of Structural Biology
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).
Eliška Koutná 💬 firstname.lastname@example.org
Project: Biological roles of LEDGF/p75 (since 2018)
Lenka Vaneková 💬 email@example.com
Project: Modulation of the STING signaling pathway (since 2018)
Lisa-Maria Weinhold 💬 firstname.lastname@example.org
Project: Structural relationship between subunits of chromatin remodeling complexes (since 2019)
Bachelor project: Detailed characterization of the interaction between LEDGF/p75 and MeCP2 (def. 2020)
Diploma project: Structural characterization of interactions between subunits of the GBAF chromatin remodeling complex (since 2020)
Project: Structural NMR studies of metabolically active proteins (def. 2019)
Practical Course in Structural Biology (MC250P76)
Structural Biology of the Cell (MB151P117)
Determination of the 3D structure of macromolecules (MC250P17)
Advanced NMR methods (MC270P08A)
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).