Abstract
The early events in the life of newly synthesized proteins in the cellular environment are remarkably complex. Concurrently with their synthesis by the ribosome, nascent polypeptides are subjected to enzymatic processing, chaperone-assisted folding or targeting to translocation pores at membranes. The ribosome itself has a key role in these different tasks and governs the interplay between the various factors involved. Indeed, the ribosome serves as a platform for the spatially and temporally regulated association of enzymes, targeting factors and chaperones that act upon the nascent polypeptides emerging from the exit tunnel. Furthermore, the ribosome provides opportunities to coordinate the protein-synthesis activity of its peptidyl transferase center with the protein targeting and folding processes. Here we review the early co-translational events involving the ribosome that guide cytosolic proteins to their native state.
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References
Bashan, A. & Yonath, A. Correlating ribosome function with high-resolution structures. Trends Microbiol. 16, 326–335 (2008).
Brandt, F. et al. The native 3D organization of bacterial polysomes. Cell 136, 261–271 (2009).
Ban, N., Nissen, P., Hansen, J., Moore, P.B. & Steitz, T.A. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 289, 905–920 (2000).
Harms, J. et al. High resolution structure of the large ribosomal subunit from a mesophilic eubacterium. Cell 107, 679–688 (2001).
Nissen, P., Hansen, J., Ban, N., Moore, P.B. & Steitz, T.A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000).
Voss, N.R., Gerstein, M., Steitz, T.A. & Moore, P.B. The geometry of the ribosomal polypeptide exit tunnel. J. Mol. Biol. 360, 893–906 (2006).
Picking, W.D., Picking, W.L., Odom, O.W. & Hardesty, B. Fluorescence characterization of the environment encountered by nascent polyalanine and polyserine as they exit Escherichia coli ribosomes during translation. Biochemistry 31, 2368–2375 (1992).
Malkin, L.I. & Rich, A. Partial resistance of nascent polypeptide chains to proteolytic digestion due to ribosomal shielding. J. Mol. Biol. 26, 329–346 (1967).
Kosolapov, A. & Deutsch, C. Tertiary interactions within the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 16, 405–411 (2009).
Lu, J., Kobertz, W.R. & Deutsch, C. Mapping the electrostatic potential within the ribosomal exit tunnel. J. Mol. Biol. 371, 1378–1391 (2007).
Lu, J. & Deutsch, C. Folding zones inside the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 12, 1123–1129 (2005).
Tsai, C.J. et al. Synonymous mutations and ribosome stalling can lead to altered folding pathways and distinct minima. J. Mol. Biol. 383, 281–291 (2008).
Crombie, T., Swaffield, J.C. & Brown, A.J.P. Protein folding within the cell is influenced by controlled rates of polypeptide elongation. J. Mol. Biol. 228, 7–12 (1992).
Komar, A.A., Lesnik, T. & Reiss, C. Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation. FEBS Lett. 462, 387–391 (1999).
Zhang, G., Hubalewska, M. & Ignatova, Z. Transient ribosomal attenuation coordinates protein synthesis and co-translational folding. Nat. Struct. Mol. Biol. 16, 274–280 (2009).
Kimchi-Sarfaty, C. et al. A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315, 525–528 (2007).
Thanaraj, T.A. & Argos, P. Protein secondary structural types are differentially coded on messenger RNA. Protein Sci. 5, 1973–1983 (1996).
Clarke, T.F., IV & Clark, P.L. Rare codons cluster. PLoS One 3, e3412 (2008).
Marin, M. Folding at the rhythm of the rare codon beat. Biotechnol. J. 3, 1047–1057 (2008).
Lu, J. & Deutsch, C. Electrostatics in the ribosomal tunnel modulate chain elongation rates. J. Mol. Biol. 384, 73–86 (2008).
Ito-Harashima, S., Kuroha, K., Tatematsu, T. & Inada, T. Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast. Genes Dev. 21, 519–524 (2007).
Dimitrova, L.N., Kuroha, K., Tatematsu, T. & Inada, T. Nascent peptide-dependent translation arrest leads to Not4p-mediated protein degradation by the proteasome. J. Biol. Chem. 284, 10343–10352 (2009).
Gong, F. & Yanofsky, C. Instruction of translating ribosome by nascent peptide. Science 297, 1864–1867 (2002).
Nakatogawa, H. & Ito, K. Secretion monitor, SecM, undergoes self-translation arrest in the cytosol. Mol. Cell 7, 185–192 (2001).
Butkus, M.E., Prundeanu, L.B. & Oliver, D.B. Translocon “pulling” of nascent SecM controls the duration of its translational pause and secretion-responsive secA regulation. J. Bacteriol. 185, 6719–6722 (2003).
Woolhead, C.A., Johnson, A.E. & Bernstein, H.D. Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. Mol. Cell 22, 587–598 (2006).
Nakatogawa, H. & Ito, K. The ribosomal exit tunnel functions as a discriminating gate. Cell 108, 629–636 (2002).
Muto, H., Nakatogawa, H. & Ito, K. Genetically encoded but nonpolypeptide prolyl-tRNA functions in the A site for SecM-mediated ribosomal stall. Mol. Cell 22, 545–552 (2006).
Fang, P., Spevak, C.C., Wu, C. & Sachs, M.S. A nascent polypeptide domain that can regulate translation elongation. Proc. Natl. Acad. Sci. USA 101, 4059–4064 (2004).
Bornemann, T., Jockel, J., Rodnina, M.V. & Wintermeyer, W. Signal sequence-independent membrane targeting of ribosomes containing short nascent peptides within the exit tunnel. Nat. Struct. Mol. Biol. 15, 494–499 (2008).
Berndt, U., Oellerer, S., Zhang, Y., Johnson, A.E. & Rospert, S. A signal-anchor sequence stimulates signal recognition particle binding to ribosomes from inside the exit tunnel. Proc. Natl. Acad. Sci. USA 106, 1398–1403 (2009).
Woolhead, C.A., McCormick, P.J. & Johnson, A.E. Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell 116, 725–736 (2004).
Evans, M.S., Sander, I.M. & Clark, P.L. Cotranslational folding promotes β-helix formation and avoids aggregation in vivo . J. Mol. Biol. 383, 683–692 (2008).
Martinez, A. et al. Extent of N-terminal modifications in cytosolic proteins from eukaryotes. Proteomics 8, 2809–2831 (2008).
Giglione, C., Boularot, A. & Meinnel, T. Protein N-terminal methionine excision. Cell. Mol. Life Sci. 61, 1455–1474 (2004).
Meinnel, T. & Giglione, C. Tools for analyzing and predicting N-terminal protein modifications. Proteomics 8, 626–649 (2008).
Ball, L.A. & Kaesberg, P. Cleavage of the N-terminal formylmethionine residue from a bacteriophage coat protein in vitro . J. Mol. Biol. 79, 531–537 (1973).
Raue, U., Oellerer, S. & Rospert, S. Association of protein biogenesis factors at the yeast ribosomal tunnel exit is affected by the translational status and nascent polypeptide sequence. J. Biol. Chem. 282, 7809–7816 (2007).
Vetro, J.A. & Chang, Y.H. Yeast methionine aminopeptidase type 1 is ribosome-associated and requires its N-terminal zinc finger domain for normal function in vivo . J. Cell. Biochem. 85, 678–688 (2002).
Zuo, S., Guo, Q., Ling, C. & Chang, Y.H. Evidence that two zinc fingers in the methionine aminopeptidase from Saccharomyces cerevisiae are important for normal growth. Mol. Gen. Genet. 246, 247–253 (1995).
Fry, K.T. & Lamborg, M.R. Amidohydrolase activity of Escherichia coli extracts with formylated amino acids and dipeptides as substrates. J. Mol. Biol. 28, 423–433 (1967).
Pine, M.J. Kinetics of maturation of the amino termini of the cell proteins of Escherichia coli . Biochim. Biophys. Acta 174, 359–372 (1969).
Adams, J.M. On the release of the formyl group from nascent protein. J. Mol. Biol. 33, 571–574 (1968).
Bingel-Erlenmeyer, R. et al. A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing. Nature 452, 108–111 (2008).
Polevoda, B. & Sherman, F. Composition and function of the eukaryotic N-terminal acetyltransferase subunits. Biochem. Biophys. Res. Commun. 308, 1–11 (2003).
Yamada, R. & Bradshaw, R.A. Rat liver polysome N α-acetyltransferase: isolation and characterization. Biochemistry 30, 1010–1016 (1991).
Green, R.M., Elce, J.S. & Kisilevsky, R. Acetylation of peptidyl-tRNA on rat liver polyribosomes. Can. J. Biochem. 56, 1075–1081 (1978).
Pestana, A. & Pitot, H.C. Acetylation of nascent polypeptide chains on rat liver polyribosomes in vivo and in vitro . Biochemistry 14, 1404–1412 (1975).
Palmiter, R.D., Gagnon, J. & Walsh, K.A. Ovalbumin: a secreted protein without a transient hydrophobic leader sequence. Proc. Natl. Acad. Sci. USA 75, 94–98 (1978).
Polevoda, B., Brown, S., Cardillo, T.S., Rigby, S. & Sherman, F. Yeast Nα-terminal acetyltransferases are associated with ribosomes. J. Cell. Biochem. 103, 492–508 (2008).
Gautschi, M. et al. The yeast Nα-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides. Mol. Cell. Biol. 23, 7403–7414 (2003).
Hartl, F.U. & Hayer-Hartl, M. Converging concepts of protein folding in vitro and in vivo . Nat. Struct. Mol. Biol. 16, 574–581 (2009).
Kramer, G. et al. L23 protein functions as a chaperone docking site on the ribosome. Nature 419, 171–174 (2002).
Maier, R., Eckert, B., Scholz, C., Lilie, H. & Schmid, F.X. Interaction of Trigger factor with the ribosome. J. Mol. Biol. 326, 585–592 (2003).
Kaiser, C.M. et al. Real-time observation of Trigger factor function on translating ribosomes. Nature 444, 455–460 (2006).
Rutkowska, A. et al. Dynamics of Trigger factor interaction with translating ribosomes. J. Biol. Chem. 283, 4124–4132 (2008).
Raine, A., Lovmar, M., Wikberg, J. & Ehrenberg, M. Trigger factor binding to ribosomes with nascent peptide chains of varying lengths and sequences. J. Biol. Chem. 281, 28033–28038 (2006).
Maier, R., Scholz, C. & Schmid, F.X. Dynamic association of Trigger factor with protein substrates. J. Mol. Biol. 314, 1181–1190 (2001).
Patzelt, H. et al. Binding specificity of Escherichia coli Trigger factor. Proc. Natl. Acad. Sci. USA 98, 14244–14249 (2001).
Deuerling, E. et al. Trigger Factor and DnaK possess overlapping substrate pools and binding specificities. Mol. Microbiol. 47, 1317–1328 (2003).
Agashe, V.R. et al. Function of Trigger factor and DnaK in multidomain protein folding: increase in yield at the expense of folding speed. Cell 117, 199–209 (2004).
Ferbitz, L. et al. Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins. Nature 431, 590–596 (2004).
Kramer, G. et al. L23 protein functions as a chaperone docking site on the ribosome. Nature 419, 171–174 (2002).
Merz, F. et al. Molecular mechanism and structure of Trigger factor bound to the translating ribosome. EMBO J. 27, 1622–1632 (2008).
Schlünzen, F. et al. The binding mode of the Trigger factor on the ribosome: implications for protein folding and SRP interaction. Structure 13, 1685–1694 (2005).
Baram, D. et al. Structure of Trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action. Proc. Natl. Acad. Sci. USA 102, 12017–12022 (2005).
Hoffmann, A. et al. Trigger factor forms a protective shield for nascent polypeptides at the ribosome. J. Biol. Chem. 281, 6539–6545 (2006).
Tomic, S., Johnson, A.E., Hartl, F.U. & Etchells, S.A. Exploring the capacity of Trigger factor to function as a shield for ribosome bound polypeptide chains. FEBS Lett. 580, 72–76 (2006).
Lakshmipathy, S.K. et al. Identification of nascent chain interaction sites on Trigger factor. J. Biol. Chem. 282, 12186–12193 (2007).
Scholz, C., Stoller, G., Zarnt, T., Fischer, G. & Schmid, F.X. Cooperation of enzymatic and chaperone functions of Trigger factor in the catalysis of protein folding. EMBO J. 16, 54–58 (1997).
Kramer, G. et al. Functional dissection of Escherichia coli Trigger factor: unraveling the function of individual domains. J. Bacteriol. 186, 3777–3784 (2004).
Merz, F. et al. The C-terminal domain of E. coli Trigger factor represents the central module of its chaperone activity. J. Biol. Chem. 42, 31963–31971 (2006).
Wiedmann, B., Sakai, H., Davis, T.A. & Wiedmann, M. A protein complex required for signal-sequence-specific sorting and translocation. Nature 370, 434–440 (1994).
Pfund, C. et al. The molecular chaperone Ssb from Saccharomyces cerevisiae is a component of the ribosome-nascent chain complex. EMBO J. 17, 3981–3989 (1998).
Gautschi, M., Mun, A., Ross, S. & Rospert, S. A functional chaperone triad on the yeast ribosome. Proc. Natl. Acad. Sci. USA 99, 4209–4214 (2002).
Wegrzyn, R.D. & Deuerling, E. Molecular guardians for newborn proteins: ribosome-associated chaperones and their role in protein folding. Cell. Mol. Life Sci. 62, 2727–2738 (2005).
Gautschi, M. et al. RAC, a stable ribosome-associated complex in yeast formed by the DnaK-DnaJ homologs Ssz1p and zuotin. Proc. Natl. Acad. Sci. USA 98, 3762–3767 (2001).
Hundley, H. et al. The in vivo function of the ribosome-associated Hsp70, Ssz1, does not require its putative peptide-binding domain. Proc. Natl. Acad. Sci. USA 99, 4203–4208 (2002).
Yan, W. et al. Zuotin, a ribosome-associated DnaJ molecular chaperone. EMBO J. 17, 4809–4817 (1998).
Albanèse, V., Yam, A.Y., Baughman, J., Parnot, C. & Frydman, J. Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124, 75–88 (2006).
Nelson, R.J., Ziegelhoffer, T., Nicolet, C., Werner-Washburne, M. & Craig, E.A. The translation machinery and 70 kDa heat shock protein cooperate in protein synthesis. Cell 71, 97–105 (1992).
Peisker, K. et al. Ribosome-associated complex binds to ribosomes in close proximity of Rpl31 at the exit of the polypeptide tunnel in yeast. Mol. Biol. Cell 19, 5279–5288 (2008).
Huang, P., Gautschi, M., Walter, W., Rospert, S. & Craig, E.A. The Hsp70 Ssz1 modulates the function of the ribosome-associated J-protein Zuo1. Nat. Struct. Mol. Biol. 12, 497–504 (2005).
Conz, C. et al. Functional characterization of the atypical Hsp70 subunit of yeast ribosome-associated complex. J. Biol. Chem. 282, 33977–33984 (2007).
Hundley, H.A., Walter, W., Bairstow, S. & Craig, E.A. Human Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous. Science 308, 1032–1034 (2005).
Otto, H. et al. The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex. Proc. Natl. Acad. Sci. USA 102, 10064–10069 (2005).
Dragovic, Z., Shomura, Y., Tzvetkov, N., Hartl, F.U. & Bracher, A. Fes1p acts as a nucleotide exchange factor for the ribosome-associated molecular chaperone Ssb1p. Biol. Chem. 387, 1593–1600 (2006).
Yam, A.Y., Albanese, V., Lin, H.T. & Frydman, J. Hsp110 cooperates with different cytosolic HSP70 systems in a pathway for de novo folding. J. Biol. Chem. 280, 41252–41261 (2005).
Raviol, H., Sadlish, H., Rodriguez, F., Mayer, M.P. & Bukau, B. Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide exchange factor. EMBO J. 25, 2510–2518 (2006).
Sondermann, H. et al. Prediction of novel Bag-1 homologs based on structure/function analysis identifies Snl1p as an Hsp70 co-chaperone in Saccharomyces cerevisiae . J. Biol. Chem. 277, 33220–33227 (2002).
Liu, Q. & Hendrickson, W.A. Insights into Hsp70 chaperone activity from a crystal structure of the yeast Hsp110 Sse1. Cell 131, 106–120 (2007).
Fünfschilling, U. & Rospert, S. Nascent polypeptide-associated complex stimulates protein import into yeast mitochondria. Mol. Biol. Cell 10, 3289–3299 (1999).
Rospert, S., Dubaquie, Y. & Gautschi, M. Nascent-polypeptide-associated complex. Cell. Mol. Life Sci. 59, 1632–1639 (2002).
Spreter, T., Pech, M. & Beatrix, B. The crystal structure of archaeal nascent polypeptide-associated complex (NAC) reveals a unique fold and the presence of a ubiquitin-associated domain. J. Biol. Chem. 280, 15849–15854 (2005).
Beatrix, B., Sakai, H. & Wiedmann, M. The α and β subunit of the nascent polypeptide-associated complex have distinct functions. J. Biol. Chem. 275, 37838–37845 (2000).
Wegrzyn, R.D. et al. A conserved motif is prerequisite for the interaction of NAC with ribosomal protein L23 and nascent chains. J. Biol. Chem. 281, 2847–2857 (2006).
Wiedmann, B., Sakai, H., Davis, T.A. & Wiedmann, M. A protein complex required for signal-sequence-specific sorting and translocation. Nature 370, 434–440 (1994).
Andersen, K.M., Semple, C.A. & Hartmann-Petersen, R. Characterisation of the nascent polypeptide-associated complex in fission yeast. Mol. Biol. Rep. 34, 275–281 (2007).
Reimann, B. et al. Initial characterization of the nascent polypeptide-associated complex in yeast. Yeast 15, 397–407 (1999).
Bloss, T.A., Witze, E.S. & Rothman, J.H. Suppression of CED-3-independent apoptosis by mitochondrial βNAC in Caenorhabditis elegans . Nature 424, 1066–1071 (2003).
Markesich, D.C., Gajewski, K.M., Nazimiec, M.E. & Beckingham, K. bicaudal encodes the Drosophila beta NAC homolog, a component of the ribosomal translational machinery* . Development 127, 559–572 (2000).
Deng, J.M. & Behringer, R.R. An insertional mutation in the BTF3 transcription factor gene leads to an early postimplantation lethality in mice. Transgenic Res. 4, 264–269 (1995).
Gasch, A.P. et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11, 4241–4257 (2000).
Craig, E.A., Eisenman, H.C. & Hundley, H.A. Ribosome-tethered molecular chaperones: the first line of defense against protein misfolding? Curr. Opin. Microbiol. 6, 157–162 (2003).
Schuwirth, B.S. et al. Structures of the bacterial ribosome at 3.5 Å resolution. Science 310, 827–834 (2005).
Pool, M.R., Stumm, J., Fulga, T.A., Sinning, I. & Dobberstein, B. Distinct modes of signal recognition particle interaction with the ribosome. Science 297, 1345–1348 (2002).
Beckmann, R. et al. Architecture of the protein-conducting channel associated with the translating 80S ribosome. Cell 107, 361–372 (2001).
Blau, M. et al. ERj1p uses a universal ribosomal adaptor site to coordinate the 80S ribosome at the membrane. Nat. Struct. Mol. Biol. 12, 1015–1016 (2005).
Halic, M. et al. Structure of the signal recognition particle interacting with the elongation-arrested ribosome. Nature 427, 808–814 (2004).
Schaffitzel, C. et al. Structure of the E. coli signal recognition particle bound to a translating ribosome. Nature 444, 503–506 (2006).
Jia, L. et al. Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C-terminal region of Oxa1. EMBO J. 22, 6438–6447 (2003).
Mitra, K. et al. Structure of the E. coli protein-conducting channel bound to a translating ribosome. Nature 438, 318–324 (2005).
Keenan, R.J., Freymann, D.M., Stroud, R.M. & Walter, P. The signal recognition particle. Annu. Rev. Biochem. 70, 755–775 (2001).
Skach, W.R. Cellular mechanisms of membrane protein folding. Nat. Struct. Mol. Biol. 16, 606–612 (2009).
Eisner, G., Koch, H.G., Beck, K., Brunner, J. & Muller, M. Ligand crowding at a nascent signal sequence. J. Cell Biol. 163, 35–44 (2003).
Eisner, G., Moser, M., Schafer, U., Beck, K. & Muller, M. Alternate recruitment of signal recognition particle and Trigger factor to the signal sequence of a growing nascent polypeptide. J. Biol. Chem. 281, 7172–7179 (2006).
Ullers, R.S. et al. Sequence-specific interactions of nascent Escherichia coli polypeptides with Trigger factor and signal recognition particle. J. Biol. Chem. 281, 13999–14005 (2006).
Ullers, R.S. et al. Interplay of signal recognition particle and Trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome. J. Cell Biol. 161, 679–684 (2003).
Raine, A., Ivanova, N., Wikberg, J.E. & Ehrenberg, M. Simultaneous binding of Trigger factor and signal recognition particle to the E. coli ribosome. Biochimie 86, 495–500 (2004).
Valent, Q.A. et al. Nascent membrane and presecretory proteins synthesized in Escherichia coli associate with signal recognition particle and Trigger factor. Mol. Microbiol. 25, 53–64 (1997).
Lee, H.C. & Bernstein, H.D. The targeting pathway of Escherichia coli presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal. Proc. Natl. Acad. Sci. USA 98, 3471–3476 (2001).
Beck, K., Wu, L.F., Brunner, J. & Muller, M. Discrimination between SRP- and SecA/SecB-dependent substrates involves selective recognition of nascent chains by SRP and Trigger factor. EMBO J. 19, 134–143 (2000).
Lee, H.C. & Bernstein, H.D. Trigger factor retards protein export in Escherichia coli . J. Biol. Chem. 277, 43527–43535 (2002).
Ullers, R.S., Ang, D., Schwager, F., Georgopoulos, C. & Genevaux, P. Trigger factor can antagonize both SecB and DnaK/DnaJ chaperone functions in Escherichia coli . Proc. Natl. Acad. Sci. USA 104, 3101–3106 (2007).
Buskiewicz, I. et al. 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 (2004).
Halic, M. et al. Following the signal sequence from ribosomal tunnel exit to signal recognition particle. Nature 444, 507–511 (2006).
Buskiewicz, I.A., Jockel, J., Rodnina, M.V. & Wintermeyer, W. Conformation of the signal recognition particle in ribosomal targeting complexes. RNA 15, 44–54 (2009).
Lauring, B., Sakai, H., Kreibich, G. & Wiedmann, M. Nascent polypeptide-associated complex protein prevents mistargeting of nascent chains to the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 92, 5411–5415 (1995).
Lauring, B., Kreibich, G. & Wiedmann, M. The intrinsic ability of ribosomes to bind to endoplasmic reticulum membranes is regulated by signal recognition particle and nascent-polypeptide-associated complex. Proc. Natl. Acad. Sci. USA 92, 9435–9439 (1995).
Möller, I. et al. A general mechanism for regulation of access to the translocon: competition for a membrane attachment site on ribosomes. Proc. Natl. Acad. Sci. USA 95, 13425–13430 (1998).
Acknowledgements
We thank members of the Bukau and Ban laboratories for critical reading of the manuscript. We acknowledge the help of Y. Cully, F. Gloge and A. Rutkowska in preparing parts of the figures. Work in the authors' laboratories is supported by grants from the Deutsche Forschungsgemeinschaft (DFG) to B.B. and G.K. (SFB 638, FOR967), the Swiss National Science Foundation (SNSF), the National Center of Excellence in Research (NCCR) Structural Biology programme of the SNSF and the ETH Research Grant TH-3/04-1 to N.B., and the Federation of European Biochemical Societies long-term fellowship to D.B.
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Kramer, G., Boehringer, D., Ban, N. et al. The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat Struct Mol Biol 16, 589–597 (2009). https://doi.org/10.1038/nsmb.1614
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DOI: https://doi.org/10.1038/nsmb.1614