Daumke Lab

My group contributes expertise in protein expression and purification and in the biophysical characterization of protein-protein and protein-ligand interactions to many groups inside and outside of the MDC. In turn, we profit from their complementary expertise in cell biology and animal experiments.

We recently supported the Haucke group at the neighboring FMP institute in determining X‑ray structures of phosphatidylinositol 3-kinase C2α to understand its activation mechanism (Lo et al., Nat Struct Mol Biol, 2022) and chemical inhibition (Lo et al., Nat Chem Biol, 2023). With Ralph Kettritz’ group (ECRC, Berlin), we examined the translational potential of monoclonal antibodies that inhibit the interaction of neutrophil receptor CD177 with its protease ligand PR3, therefore reducing neutrophil activation (Marino et al., J Biol Chem, 2022). With the Schürmann group at the German Institute for Nutrition Research in Potsdam, we identified the scaffolding protein GOPC as a cellular binding partner for the small GTPase ARFRP1 and a function of the complex in insulin secretion (Wilhelmi et al., Mol Metab, 2021). With the Winkelmann group at HMGU in Munich, we biochemically characterized mutants of a key purine biosynthetic enzyme, IMPDH2, which lead dystonia, a neurological movement disorder (Zech et al., Lancet Neurol, 2020). With the Krauss group at FMP, we biochemically characterized the septin1 GTPases to identify a role in maintaining Golgi integrity (Song et al., J Cell Sci, 2019). Together with the DiVirgilio group/MDC, we characterized the assembly of 53BP1 to dissect its function in immunoglobin class switch recombination and DNA double strand break protection (Sundaravinayagam et al., Cell Rep, 2019). We also supported the Klussmann and Scheidereit groups at the MDC with biochemical experiments to characterize an AKAP-Lbc-RhoA interaction inhibitor (Schrade et al., PloS One, 2018) and a lymphotoxin-α mediated autocrine signaling pathway (von Hoff et al., Blood, 2019), respectively.

References

1. Lo, W.T., Zhang, Y., Vadas, O., Roske, Y., Gulluni, F., De Santis, M.C., Zagar, A.V., Stephanowitz, H., Hirsch, E., Liu, F., et al. (2022). Structural basis of phosphatidylinositol 3-kinase C2α function. Nat Struct Mol Biol 29, 218-228. https://doi.org/10.1038/s41594-022-00730-w.
2. Lo, W.T., Belabed, H., Kücükdisli, M., Metag, J., Roske, Y., Prokofeva, P., Ohashi, Y., Horatscheck, A., Cirillo, D., Krauss, M., et al. (2023). Development of selective inhibitors of phosphatidylinositol 3-kinase C2α. Nat Chem Biol 19, 18-27. https://doi.org/10.1038/s41589-022-01118-z.
3. Marino, S.F., Jerke, U., Rolle, S., Daumke, O., and Kettritz, R. (2022). Competitively disrupting the neutrophil-specific receptor-autoantigen CD177:proteinase 3 membrane complex reduces anti-PR3 antibody-induced neutrophil activation. J Biol Chem 298, 101598. https://doi.org/10.1016/j.jbc.2022.101598.
4. Wilhelmi, I., Grunwald, S., Gimber, N., Popp, O., Dittmar, G., Arumughan, A., Wanker, E.E., Laeger, T., Schmoranzer, J., Daumke, O., and Schürmann, A. (2021). The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic β-cells. Mol Metab 45, 101151. https://doi.org/10.1016/j.molmet.2020.101151.
5. Zech, M., Jech, R., Boesch, S., Škorvánek, M., Weber, S., Wagner, M., Zhao, C., Jochim, A., Necpál, J., Dincer, Y., et al. (2020). Monogenic variants in dystonia: an exome-wide sequencing study. Lancet Neurol 19, 908-918. https://doi.org/10.1016/s1474-4422(20)30312-4.
6. Song, K., Gras, C., Capin, G., Gimber, N., Lehmann, M., Mohd, S., Puchkov, D., Rodiger, M., Wilhelmi, I., Daumke, O., et al. (2019). A SEPT1-based scaffold is required for Golgi integrity and function. J Cell Sci 132. https://doi.org/10.1242/jcs.225557.
7. Sundaravinayagam, D., Rahjouei, A., Andreani, M., Tupina, D., Balasubramanian, S., Saha, T., Delgado-Benito, V., Coralluzzo, V., Daumke, O., and Di Virgilio, M. (2019). 53BP1 Supports Immunoglobulin Class Switch Recombination Independently of Its DNA Double-Strand Break End Protection Function. Cell Rep 28, 1389-1399.e1386. https://doi.org/10.1016/j.celrep.2019.06.035.
8. Schrade, K., Troger, J., Eldahshan, A., Zuhlke, K., Abdul Azeez, K.R., Elkins, J.M., Neuenschwander, M., Oder, A., Elkewedi, M., Jaksch, S., et al. (2018). An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells. PloS One 13, e0191423. https://doi.org/10.1371/journal.pone.0191423.
9. von Hoff, L., Kärgel, E., Franke, V., McShane, E., Schulz-Beiss, K.W., Patone, G., Schleussner, N., Kolesnichenko, M., Hübner, N., Daumke, O., et al. (2019). Autocrine LTA signaling drives NF-κB and JAK-STAT activity and myeloid gene expression in Hodgkin lymphoma. Blood 133, 1489-1494. https://doi.org/10.1182/blood-2018-08-871293.