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Efficient production of functional proteins is vital for cellular activity. Newly synthesized polypeptides undergo processing, folding, assembly into complexes, and membrane targeting. These steps are often closely coupled to mRNA translation by ribosomes and facilitated by specialized machinery that dynamically interacts with nascent chains at specific translation stages. Tailoring these interactions to the unique requirements of each protein is a major challenge yet essential for maintaining cellular proteostasis.
Our research focuses on understanding how cells coordinate translation with protein maturation. Specifically, we investigate (i) mechanisms regulating local translation speed by ribosomes, (ii) how these variations influence nascent chain interactions for folding, assembly, and interactions with chaperones and targeting factors, and (iii) how cells co-translationally recognize and target proteins to organelles such as the ER and mitochondria.
To address these questions, we utilize a diverse range of model systems, including bacteria, yeast, and mammalian cells. In addition to using established molecular biology and biochemistry techniques, we develop innovative deep-sequencing approaches that enable us to systematically study ribosome and nascent chain interactions within living cells.
Selected
publications
Original
Papers
1. Eismann, L., Fijalkowski, I., Galmozzi, C. V., Koubek, J., Tippmann, F., Van Damme, P. & Kramer, G. (2022) Selective ribosome profiling reveals a role for SecB in the co-translational inner membrane protein biogenesis. Cell Rep 41, 111776. 10.1016/j.celrep.2022.111776.
2. Bertolini, M., Fenzl, K., Kats, I., Wruck, F., Tippmann, F., Schmitt, J., Auburger, J. J., Tans, S., Bukau, B.# & Kramer, G.# (2021) Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly. Science 371, 57-64. 10.1126/science.abc7151.
3. Galmozzi, C. V., Merker, D., Friedrich, U. A., Doring, K. & Kramer, G. (2019) Selective ribosome profiling to study interactions of translating ribosomes in yeast. Nat Protoc 14, 2279-2317. 10.1038/s41596-019-0185-z.
4. Shiber, A., Doring, K., Friedrich, U., Klann, K., Merker, D., Zedan, M., Tippmann, F., Kramer, G.# & Bukau, B.# (2018) Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling. Nature 561, 268-272. 10.1038/s41586-018-0462-y.
5. Doring, K., Ahmed, N., Riemer, T., Suresh, H. G., Vainshtein, Y., Habich, M., Riemer, J., Mayer, M. P., O'Brien, E. P., Kramer, G.# & Bukau, B.# (2017) Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding. Cell 170, 298-311 e220. 10.1016/j.cell.2017.06.038.
6. Schibich, D., Gloge, F., Pohner, I., Bjorkholm, P., Wade, R. C., von Heijne, G., Bukau, B.# & Kramer, G.# (2016) Global profiling of SRP interaction with nascent polypeptides. Nature 536, 219-223. 10.1038/nature19070.
7. Shieh, Y. W., Minguez, P., Bork, P., Auburger, J. J., Guilbride, D. L., Kramer, G.# & Bukau, B.# (2015) Operon structure and cotranslational subunit association direct protein assembly in bacteria. Science 350, 678-680. 10.1126/science.aac8171.
8. Sandikci, A., Gloge, F., Martinez, M., Mayer, M. P., Wade, R., Bukau, B.# & Kramer, G.# (2013) Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding. Nat Struct Mol Biol 20, 843-850. 10.1038/nsmb.2615.
9. Hoffmann, A., Becker, A. H., Zachmann-Brand, B., Deuerling, E., Bukau, B.# & Kramer, G.# (2012) Concerted action of the ribosome and the associated chaperone trigger factor confines nascent polypeptide folding. Mol Cell 48, 63-74. 10.1016/j.molcel.2012.07.018.
10. Kramer, G., Rauch, T., Rist, W., Vorderwulbecke, S., Patzelt, H., Schulze-Specking, A., Ban, N., Deuerling, E. & Bukau, B. (2002) L23 protein functions as a chaperone docking site on the ribosome. Nature 419, 171-174. 10.1038/nature01047.
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