Publications

2023: New publication in Science

Control of protein interactions with the ribosome by NAC

  

The molecular control centre of our protein factories

Researchers from Konstanz and Zurich headed by Elke Deuerling have deciphered a biochemical mechanism that ensures that newly formed proteins are processed correctly when they leave the cell's own protein factories.

Up to now, it was unclear how methionine aminopeptidases (METAPs) come into contact with the protein factories and, just at the right place and moment, cause the excision of methionine from specific proteins. Access of METAPs to protein factories is controlled by a "ribosomal gatekeeper" called NAC (short for "nascent polypeptide-associated complex").

Biologists Elke Deuerling, Martin Gamerdinger and their team from the University of Konstanz (Germany), together with Nenad Ban and his colleagues from ETH Zurich (Switzerland), have now shed light on the subject.

The results have been published in Science, see also the press release by the University of Konstanz.


2022: New publication in Science

    

Control of protein sorting at the ribosome by NAC

The gatekeeper of the protein factory

The long-standing riddle on how proteins are sorted to their correct destination inside the cell already during their biosynthesis in the ribosome has been solved by an international consortium of scientists headed by Elke Deuerling from the University of Konstanz.

This process is controlled by the "nascent-polypeptide-associated complex" NAC - the molecular mechanism underlying correct sorting have been clarified by Elke Deuerling and her group in collaboration with scientists from the ETH Zurich in Switzerland, the MRC Laboratory in Cambridge in the U.K, and the Caltech in Pasadena in the U.S.A.

The results are published in Science, see also the press release by the University of Konstanz


Publication list

  • ­­Gamerdinger, M., and Deuerling, E. (2023) Cotranslational sorting and processing of newly synthesized proteins in eukaryotes. Trends Biochem. Sci., epub ahead of print short | full
  • Gamerdinger, M., Jia, M., Schloemer, R., Rabl, L., Jaskolowski, M., Khakzar, K.M., Ulusoy, Z., Wallisch, A., Jomaa, A., Hunaeus, G., Scaiola, A., Diederichs, K., Ban, N., and Deuerling, E. (2023) NAC controls cotranslational N-terminal methionine excision in eukaryotes. Science 380, 1238–1243 short | full
  • Jaskolowski, M., Ahmad Jomaa, A., Gamerdinger, M., Shrestha, S., Leibundgut, M., Deuerling, E., and Ban, N. (2023) Molecular basis of the TRAP complex function in ER protein biogenesis. Nat. Struct. Mol. Biol., published online 11/05/2023 short | full
  • Jomaa, A., Gamerdinger, M., Hsieh, H.-H., Wallisch, A., Chandrasekaran, V., Ulusoy, Z., Scaiola, A., Hegde, R.S., Shan, S.-O., Ban, N., and Deuerling, E. (2022) Mechanism of signal sequence handover from NAC to SRP on ribosomes during ER-protein targeting. Science 375, 839-844 short | full
  • Fries, S., Braun, T.S., Globisch, C., Peter, C., Drescher, M., and Deuerling, E. (2021) Deciphering molecular details of the RAC–ribosome interaction by EPR spectroscopy. Sci. Rep. 11, 8681 full
  • Nikolay, R., Hilal, T., Schmidt, S., Qin, B., Schwefel, D., Vieira-Vieira, C.H., Mielke, T., Bürger, J., Loerke, J., Amikura, K., Flügel, T., Ueda, T., Selbach, M., Deuerling, E., and Spahn, C.M.T. (2021) Snapshots of native pre-50S ribosomes reveal a biogenesis factor network and evolutionary specialization. Mol. Cell 81, 1200-1215 short | full
  • Fürsch, J., Kammer, K.M., Kreft, S.G., Beck, M., and Stengel, F. (2020) Proteome-wide structural probing of low-abundant protein interactions by cross-linking mass spectrometry. Anal. Chem. 92, 4016-4022 short | full
  • Schneider, T., Berg, A., Ulusoy, Z., Gamerdinger, M., Peter, C., and Kovermann, M. (2019) Conformational and functional characterization of artificially conjugated non-canonical ubiquitin dimers. Sci. Rep. 9, 19991 short | full
  • Gamerdinger, M., Kobayashi, K., Wallisch, A., Kreft, S.G., Sailer, C., Schlömer, R., Sachs, N., Jomaa, A., Stengel, F., Ban, N., and Deuerling, E. (2019) Early scanning of nascent polypeptides inside the ribosomal tunnel by NAC. Mol. Cell 75, 996-1006  short recommended in F1000Prime as being of special significance in its field
  • Shen, K., Gamerdinger, M., Chan, R., Gense, K., Martin, E.M., Sachs, N., Knight, P.D., Schlömer, R., Calabrese, A.N., Stewart, K.L., Leiendecker, L., Baghel, A., Radford, S.E., Frydman, J., and Deuerling, E. (2019) Dual role of ribosome-binding domain of NAC as a potent suppressor of protein aggregation and aging-related proteinopathies. Mol. Cell 74, 729-741 short | full
  • Sack, M., Stifel, J., Kreft, S.G., Deuerling, E., and Hartig, J. (2019) Neomycin-dependent hammerhead ribozymes for the direct control of gene expression in Saccharomyces cerevisiae. Methods 161, 35-40 short | full
  • Deuerling, E., Gamerdinger, M., and Kreft, S.G. (2019) Chaperone interactions at the ribosome. Cold Spring Harb. Perspect. Biol. 11, a033977 short
  • Wurmthaler, L.A., Sack, M., Gense, K., Hartig, J., and Gamerdinger, M. (2019) A tetracycline-dependent ribozyme switch allows conditional induction of gene expression in Caenorhabditis elegans. Nat. Commun. 10, 491 short | full
  • Martin, E.M., Jackson, M.P., Gamerdinger, M., Gense, K., Karamanos, T.K., Humes, J.R., Deuerling, E., Ashcroft, A.E., and Radford, S.E. (2018) Conformational flexibility within the nascent polypeptide-associated complex enables its interactions with structurally diverse client proteins. J. Biol. Chem. 293, 8554-8568 short | full
  • Yushchenko, T., Deuerling, E., and Hauser, K. (2018) Insights into the aggregation mechanism of polyQ proteins with different glutamine repeat lengths. Biophys. J. 114, 1847-1857 short | full
  • Kreft, S., and Deuerling, E. (2018) Vms1: A cytosolic CAT-tailing antagonist to protect mitochondria.  Trends Cell Biol. 28, 3-5 short | full
  • Gamerdinger, M. (2016) Protein quality control at the ribosome: focus on RAC, NAC and RQC. Essays Biochem. 60, 203-212 short | full
  • Hanebuth, M.A., Kityk, R., Fries, S.J., Jain, A., Kriel, A., Albanese, V., Frickey, T., Peter, C., Mayer, M.P., Frydman, J., and Deuerling, E. (2016) Multivalent contacts of the Hsp70 Ssb contribute to its architecture on ribosomes and nascent chain interaction. Nat. Commun. 7, 13695 short | full
  • Nikolay, R., Schmidt, S., Schlömer, R., Deuerling, E., and Nierhaus, K. (2016) Ribosome assembly as antimicrobial target. Antibiotics 5, 18 short | full
  • Ott, A.-K., Locher, L., Koch, M. and Deuerling, E. (2015) Functional dissection of the nascent polypeptide-associated complex in Saccharomyces cerevisiae. PLoS One, e0143457 short | full
  • Rajabi, K., Reuther, J., Deuerling, E., Radford, S.E., and Ashcroft, A.E. (2015) A comparison of the folding characteristics of free and ribosome-tethered polypeptide chains using limited proteolysis and mass spectrometry. Protein Sci. 24, 1282-1291 short | full
  • Preissler, S., Reuther, J., Koch, M., Scior, A., Bruderek, M., Frickey, T., and Deuerling, E. (2015) Not4-dependent translation repression is important for cellular protein homeostasis in yeast. EMBO J. 34, 1905-1924 short | full
  • Gamerdinger, M., Hanebuth, M.A., Frickey, T., and Deuerling, E. (2015) The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum. Science 348, 201-207 short | full
  • Deuerling, E., and Nikolay, R. (2015) Fluorosomen werfen Licht auf Ribosomenproduktion. BioSpektrum 21, 164-166 full
  • Nikolay, R., Schlömer, R., Müller, S., and Deuerling, E. (2015) Fluorescence-based monitoring of ribosome assembly landscapes. BMC Mol. Biol. 16, 3 full
  • Gamerdinger, M., and Deuerling, E. (2014) Trigger Factor flexibility. Science 344:590-591 full
  • Nikolay, R., Schlömer, R., Schmidt, S., Müller, S., Heubach, A., and Deuerling, E. (2014) Validation of a fluorescence-based screening concept to identify ribosome assembly defects in Escherichia coli. Nucleic Acids Res. 42, e100 short | full
  • Scior, A., and Deuerling, E. (2014) Functions of ribosome-associated chaperones and their interaction network. In: Houry W, (ed) The molecular chaperones interaction networks in protein folding and degradation. New York: Springer; pp 27-51
  • Kirstein-Miles, J., Scior, A., Deuerling, E., and Morimoto RI (2013) The nascent polypeptide associated complex is a key regulator of proteostasis. EMBO J. 32, 1451-1468, short | full
  • Gamerdinger, M., and Deuerling, E. (2012) Macrolides: the plug is out. Cell 151, 469 short | full
  • Basters, A., Ketscher, L., Deuerling, E., Arkona, C., Rademann, J., Knobeloch, K.-P., and Fritz, G. (2012) High yield expression of catalytically active USP18 using a Trigger Factor fusion system. BMC Biotechnology 12, 56 short | full
  • Hoffmann, A., Becker, A.H., Zachmann-Brand, B., Deuerling, E., Bukau, B., and Kramer, G. (2012) Concerted action of the ribosome and the associated chaperone Trigger Factor confines nascent polypeptide folding. Mol. Cell 48, 63 short | full
  • Juretschke, J., and Deuerling, E. (2012) Ribosom-assoziierte Chaperone kontrollieren die Proteinbiosynthese. Biospektrum 2, 152-155 short
  • Preissler, S., and Deuerling, E. (2012) Ribosome-associated chaperones as key players in proteostasis. Trends Biochem. Sci. 37, 274-283 short | full
  • Scior, A., Preissler, S., Koch, M., and Deuerling, E. (2011) Directed PCR-free engineering of highly repetitive DNA sequences. BMC Biotechnology, 11, 87 short | full
  • Eichmann, C., Preissler, S., Riek, R., and Deuerling, E. (2010) Co-translational structure acquisition of nascent polypeptides monitored by NMR spectroscopy. Proc. Natl. Acad. Sci. USA 107, 9111-9116 full
  • Erhardt, M., Wegrzyn, R.D., and Deuerling, E. (2010) Extra N-terminal residues have a profound effect on the aggregation properties of the potential yeast prion protein Mca1. PLoS ONE 5, e9929 full
  • Koplin, A., Preissler, S., Ilina, Y., Koch, M., Scior, A., Erhardt, M., and Deuerling, E. (2010) A dual function for chaperones Ssb/RAC and the NAC nascent polypeptide-associated complex on ribosomes. J. Cell Biol. 189, 57-68 short | full
  • Fiaux, J., Horst, J., Scior, A., Preissler, S., Koplin, A., Bukau, B., and Deuerling, E. (2010) Structural analysis of the ribosome-associated complex (RAC) reveals an unusual Hsp70/Hsp40 interaction. J. Biol. Chem. 285, 3227–3234 short | full
  • Rutkowska, A., Mayer, M. P., Hoffmann, A., Merz, F., Zachmann-Brand, B., Schaffitzel, C., Ban, N., Deuerling, E., and Bukau, B. (2008) Dynamics of Trigger Factor interaction with translating ribosomes. J. Biol. Chem. 283, 4124-4132 short | full
  • Merz, F., Boehringer, D., Schaffitzel, C., Preißler, S., Hoffmann, A., Maier, T., Rutkowska, A., Lozza, J., Ban, N., Bukau, B., and Deuerling, E. (2008) Molecular mechanism and structure of Trigger Factor bound to the translating ribosome. EMBO J. 27, 1622-1632 short | full
  • de Marco, A., Deuerling, E., Mogk, A., Tomoyasu, T., and Bukau, B. (2007) Chaperone-based procedure to increase yields of soluble recombinant proteins produced in E. coli. BMC Biotechnology 7, 32 short | full
  • Merz, F., Hoffmann, A., Rutkowska, A., Zachmann-Brand, B., Bukau, B., and Deuerling, E. (2006) The C-terminal domain of E. coli Trigger Factor represents the central module of its chaperone activity. J. Biol. Chem. 281, 31963-31971 short | full
  • Hoffmann, A., Merz, F., Rutkowska, A., Zachmann-Brand, B., Deuerling, E., and Bukau, B. (2006) Trigger factor forms a protective shield for nascent polypeptides at the ribosome. J. Biol. Chem. 281, 6539-6545 short | full
  • Wegrzyn, R. D., Hofmann, D., Merz, F., Nikolay, R., Rauch, T., Graf, C., and Deuerling, E. (2006) A conserved motif is prerequisite for the interaction of NAC with ribosomal protein L23 and nascent chains. J. Biol. Chem. 281, 2847-2857 short | full
  • Rauch, T., Hundley, H. A., Pfund, C., Wegrzyn, R. D., Walter, W., Kramer, G., Kim, S. Y., Craig, E. A., and Deuerling, E. (2005) Dissecting functional similarities of ribosome-associated chaperones from yeast and Escherichia coli. Mol. Microbiol. 57, 357-365 short | full
  • Wegrzyn, R.D., Deuerling, E. (2005) Molecular guardians for newborn proteins: ribosome-associated chaperones and their role in protein folding. Cell Mol. Life Sci. 62, 2727-2738 short | full
  • Henrichs, T., Mikhaleva, N., Conz, C., Deuerling, E., Boyd, D., Bibi, E., and Ehrmann, M. (2005) Target-directed proteolysis at the ribosome. Proc. Natl. Acad. Sci. USA 102, 4246-4251 short | full
  • Vorderwülbecke, S., Kramer, G., Merz, F., Kurz, T. A., Rauch, T., Zachmann-Brand, B., Bukau, B., and Deuerling, E. (2004) Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking Trigger Factor and DnaK. FEBS Lett. 559, 181-187 short | full
  • Ferbitz, L., Maier, T., Patzelt, H., Bukau, B., Deuerling, E. and Ban, N. (2004) Trigger Factor in complex with the ribosome forms a molecular cradle for nascent proteins. Nature 431, 590-596 short | full
  • Kramer, G., Patzelt, H., Rauch, T., Kurz, T. A., Vorderwülbecke, S., Bukau, B. and Deuerling, E. (2004) Trigger Factor’s peptidyl-prolyl cis/trans isomerase activity is not essential for the folding of cytosolic proteins in Escherichia coli. J. Biol. Chem. 279, 14165-14170 short | full
  • Kramer, G., Rutkowska, A., Wegrzyn, R., Patzelt, H., Kurz, T. A., Merz, F., Rauch, T., Vorderwülbecke, S., Deuerling, E., and Bukau, B. (2004) Functional dissection of Escherichia coli Trigger Factor: Unravelling the function of individual domains. J. Bacteriol. 186, 3777-3784 short | full
  • Buskiewicz,I., Deuerling, E., Gu, S.-Q., Jöckel, J., Rodnina, M. V., Bukau B., and Wintermeyer, W. (2004) Trigger factor binds to ribosome-signal-recognition particle (SRP) complexes and is excluded by binding of the SRP receptor. Proc. Natl. Acad. Sci. USA 101, 7902-7906 short | full
  • Dumitru, G. L., Groemping, Y., Klostermeier, D., Restle, T., Deuerling, E., and Reinstein, J. (2004) DafA cycles between the DnaK chaperone system and translational machinery. J. Mol. Biol. 339, 1179-1189 short | full
  • Deuerling, E., Patzelt, H., Vorderwülbecke, S., Rauch, T., Kramer, G., Schaffitzel, E., Mogk, A., Schulze-Specking, A., Langen, H., and Bukau, B. (2003) Trigger Factor and DnaK possess overlapping substrate pools and binding specificities. Mol. Microbiol. 47, 1317-1328 short | full
  • Kobayashi, K., Ehrlich, S.D, Albertin,i A., Amati, G., Andersen, K.K., Arnaud, M., Asai, K., Ashikaga, S., Aymerich, S., Bessieres, P., Boland, F., Brignell, S. C., Bron, S., Bunai, K., Chapuis, J., Christiansen, L.C., Danchin, A., Débarbouillé M., Dervyn E., Deuerling E., et al., (2003) Essential Bacillus subtilis genes. Proc. Natl. Acad. Sci. USA 100, 4678-4683 short | full
  • Mogk, A., Deuerling, E., Vorderwühlbecke, S., Vierling, E., and Bukau, B. (2003) Small heat shock proteins, ClpB and the DnaK system in reversing protein aggregation. Mol. Microbiol. 50, 585-595 short | full
  • Kramer, G., Rauch, T., Rist, W. Vorderwülbecke, S., Patzelt, H., Schulze-Specking, A., Ban, N., Deuerling, E., and Bukau, B. (2002) L23 protein functions as a chaperone docking site on the ribosome. Nature 419, 171-174 short | full
  • Patzelt, H., Kramer, G., Rauch,T., Schönfeld, H.-J., Bukau, B., and Deuerling, E. (2002) Three state equilibrium of Escherichia coli Trigger Factor. Biol. Chem. 383, 1611-1619 short | full
  • Schaffitzel, E., Rüdiger, S., Bukau, B., and Deuerling, E. (2001) Functional dissection of Trigger Factor and DnaK: Interactions with nascent polypeptides and thermally denatured proteins. Biol. Chem. 382, 1235-1243 short | full
  • Patzelt, H., Rüdiger, S., Brehmer, D., Kramer, G., Vorderwülbecke, S., Schaffitzel, E., Waitz, A., Hesterkamp, T., Dong, L. Schneider-Mergener, J., Bukau, B., and Deuerling, E. (2001) Binding specificity of Escherichia coli Trigger Factor. Proc. Natl. Acad. Sci. USA 98, 14244-14249 short | full
  • Bukau et al., (2000). Getting newly synthesized proteins into shape. Cell 101, 119-122 full
  • Deuerling, E., Schulze-Specking, A., Tomoyasu, T., Mogk, A., and Bukau, B. (1999) Trigger Factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400, 693-696 short | full
  • Hesterkamp, T., Deuerling, E., and Bukau, B. (1997) The amino-terminal 118 amino acids of Escherichia coli Trigger Factor constitute a domain that is necessary and sufficient for binding to ribosomes. J. Biol. Chem. 272, 21865-21871 short | full
  • Deuerling, E., Mogk, A., Richter, C., Purucker, M., and Schumann, W. (1997) The ftsH gene of Bacillus subtilis is involved in major cellular processes such as sporulation, stress adaptation and secretion. Mol. Microbiol. 23, 921-933 short
  • Deuerling, E., Paeslack, B., and Schumann, W. (1995) The ftsH gene of Bacillus subtilis is transiently induced after osmotic and temperature upshift. J. Bacteriol. 177, 4105-4112 short | full