PDBsum entry 1w26

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protein Protein-protein interface(s) links
Chaperone PDB id
Protein chains
432 a.a. *
Waters ×88
* Residue conservation analysis
PDB id:
Name: Chaperone
Title: Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins
Structure: Trigger factor. Chain: a, b. Synonym: tf. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
2.7Å     R-factor:   0.241     R-free:   0.324
Authors: L.Ferbitz,T.Maier,H.Patzelt,B.Bukau,E.Deuerling,N.Ban
Key ref:
L.Ferbitz et al. (2004). Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins. Nature, 431, 590-596. PubMed id: 15334087 DOI: 10.1038/nature02899
28-Jun-04     Release date:   02-Sep-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A850  (TIG_ECOLI) -  Trigger factor
432 a.a.
432 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylproline (omega=180) = peptidylproline (omega=0)
Peptidylproline (omega=180)
= peptidylproline (omega=0)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     cell cycle   6 terms 
  Biochemical function     protein binding involved in protein folding     6 terms  


    Added reference    
DOI no: 10.1038/nature02899 Nature 431:590-596 (2004)
PubMed id: 15334087  
Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins.
L.Ferbitz, T.Maier, H.Patzelt, B.Bukau, E.Deuerling, N.Ban.
During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosome-associated chaperones, which assist their folding to the native state. Here we present a 2.7 A crystal structure of Escherichia coli trigger factor, the best-characterized chaperone of this type, together with the structure of its ribosome-binding domain in complex with the Haloarcula marismortui large ribosomal subunit. Trigger factor adopts a unique conformation resembling a crouching dragon with separated domains forming the amino-terminal ribosome-binding 'tail', the peptidyl-prolyl isomerase 'head', the carboxy-terminal 'arms' and connecting regions building up the 'back'. From its attachment point on the ribosome, trigger factor projects the extended domains over the exit of the ribosomal tunnel, creating a protected folding space where nascent polypeptides may be shielded from proteases and aggregation. This study sheds new light on our understanding of co-translational protein folding, and suggests an unexpected mechanism of action for ribosome-associated chaperones.
  Selected figure(s)  
Figure 2.
Figure 2: Structure of the trigger factor bound to the 50S ribosomal subunit. a, Overview of the trigger factor 50S complex. Full-length trigger factor positioned by superimposition onto the ribosome-bound fragment trigger factor 1 -144 is shown as C[ ]-trace together with a slice of 50S along the peptide exit tunnel (for clarity, further cavities peripheral to the tunnel are not shown) with a modelled nascent chain in magenta, extending from the peptidyl transferase centre (PT). Colouring is as in Fig. 1. Inset: schematic footprints of Sec61, SRP and the trigger factor on the ribosome on the basis of crystallographic and electron microscopic data. Binding sites for Sec61p (blue), SRP (magenta) and the trigger factor (red) are represented as filled areas, and projections of the molecules are shown as outlines in the same colours. Positions of selected ribosomal proteins are indicated in the same colours as in Fig. 1. b, c, Close-up side (b) and top (c) views of the complex shown in a without a nascent peptide.
Figure 3.
Figure 3: Trigger factor exposes a hydrophobic cradle to the nascent chain. a, Solvent accessible surface of trigger factor (in stereo view), coloured by electrostatic potential (blue, positive; red, negative). b, C[ ]-trace representation of trigger factor with approximate dimensions of the cradle indicated; coloured according to Fig. 1.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 431, 590-596) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21370971 D.V.Fedyukina, and S.Cavagnero (2011).
Protein folding at the exit tunnel.
  Annu Rev Biophys, 40, 337-359.  
21776078 F.U.Hartl, A.Bracher, and M.Hayer-Hartl (2011).
Molecular chaperones in protein folding and proteostasis.
  Nature, 475, 324-332.  
20439768 C.Eichmann, S.Preissler, R.Riek, and E.Deuerling (2010).
Cotranslational structure acquisition of nascent polypeptides monitored by NMR spectroscopy.
  Proc Natl Acad Sci U S A, 107, 9111-9116.  
20797628 F.Brandt, L.A.Carlson, F.U.Hartl, W.Baumeister, and K.Grünewald (2010).
The three-dimensional organization of polyribosomes in intact human cells.
  Mol Cell, 39, 560-569.  
20487556 H.Hartman, and T.F.Smith (2010).
GTPases and the origin of the ribosome.
  Biol Direct, 5, 36.  
21087465 J.C.Ahn, D.W.Kim, Y.N.You, M.S.Seok, J.M.Park, H.Hwang, B.G.Kim, S.Luan, H.S.Park, and H.S.Cho (2010).
Classification of rice (Oryza sativa L. Japonica nipponbare) immunophilins (FKBPs, CYPs) and expression patterns under water stress.
  BMC Plant Biol, 10, 253.  
20371331 K.G.Ugrinov, and P.L.Clark (2010).
Cotranslational folding increases GFP folding yield.
  Biophys J, 98, 1312-1320.  
20071467 L.Müller, Escauriaza, P.Lajoie, M.Theis, M.Jung, A.Müller, C.Burgard, M.Greiner, E.L.Snapp, J.Dudek, and R.Zimmermann (2010).
Evolutionary gain of function for the ER membrane protein Sec62 from yeast to humans.
  Mol Biol Cell, 21, 691-703.  
20204450 S.J.Facey, and A.Kuhn (2010).
Biogenesis of bacterial inner-membrane proteins.
  Cell Mol Life Sci, 67, 2343-2362.  
19809489 A.Hoffmann, and B.Bukau (2009).
Trigger factor finds new jobs and contacts.
  Nat Struct Mol Biol, 16, 1006-1008.  
19647435 C.Giglione, S.Fieulaine, and T.Meinnel (2009).
Cotranslational processing mechanisms: towards a dynamic 3D model.
  Trends Biochem Sci, 34, 417-426.  
19737520 E.Martinez-Hackert, and W.A.Hendrickson (2009).
Promiscuous substrate recognition in folding and assembly activities of the trigger factor chaperone.
  Cell, 138, 923-934.
PDB codes: 3gty 3gu0
19491934 F.U.Hartl, and M.Hayer-Hartl (2009).
Converging concepts of protein folding in vitro and in vivo.
  Nat Struct Mol Biol, 16, 574-581.  
19491936 G.Kramer, D.Boehringer, N.Ban, and B.Bukau (2009).
The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins.
  Nat Struct Mol Biol, 16, 589-597.  
19234698 H.J.Moon, M.Jeya, I.S.Yu, J.H.Ji, D.K.Oh, and J.K.Lee (2009).
Chaperone-aided expression of LipA and LplA followed by the increase in alpha-lipoic acid production.
  Appl Microbiol Biotechnol, 83, 329-337.  
19029307 I.A.Buskiewicz, J.Jöckel, M.V.Rodnina, and W.Wintermeyer (2009).
Conformation of the signal recognition particle in ribosomal targeting complexes.
  RNA, 15, 44-54.  
19569194 J.P.Ellis, P.H.Culviner, and S.Cavagnero (2009).
Confined dynamics of a ribosome-bound nascent globin: Cone angle analysis of fluorescence depolarization decays in the presence of two local motions.
  Protein Sci, 18, 2003-2015.  
19173718 O.Kolaj, S.Spada, S.Robin, and J.G.Wall (2009).
Use of folding modulators to improve heterologous protein production in Escherichia coli.
  Microb Cell Fact, 8, 9.  
19004020 O.Kurkcuoglu, Z.Kurkcuoglu, P.Doruker, and R.L.Jernigan (2009).
Collective dynamics of the ribosomal tunnel revealed by elastic network modeling.
  Proteins, 75, 837-845.  
19920179 R.P.Jakob, G.Zoldák, T.Aumüller, and F.X.Schmid (2009).
Chaperone domains convert prolyl isomerases into generic catalysts of protein folding.
  Proc Natl Acad Sci U S A, 106, 20282-20287.  
19633874 V.B.V Rajan, and P.D'Silva (2009).
Arabidopsis thaliana J-class heat shock proteins: cellular stress sensors.
  Funct Integr Genomics, 9, 433-446.  
18045873 A.Rutkowska, M.P.Mayer, A.Hoffmann, F.Merz, B.Zachmann-Brand, C.Schaffitzel, N.Ban, E.Deuerling, and B.Bukau (2008).
Dynamics of trigger factor interaction with translating ribosomes.
  J Biol Chem, 283, 4124-4132.  
18478103 E.Angov, C.J.Hillier, R.L.Kincaid, and J.A.Lyon (2008).
Heterologous protein expression is enhanced by harmonizing the codon usage frequencies of the target gene with those of the expression host.
  PLoS ONE, 3, e2189.  
18497744 F.Merz, D.Boehringer, C.Schaffitzel, S.Preissler, A.Hoffmann, T.Maier, A.Rutkowska, J.Lozza, N.Ban, B.Bukau, and E.Deuerling (2008).
Molecular mechanism and structure of Trigger Factor bound to the translating ribosome.
  EMBO J, 27, 1622-1632.
PDB code: 2vrh
17680696 H.M.Lu, and J.Liang (2008).
A model study of protein nascent chain and cotranslational folding using hydrophobic-polar residues.
  Proteins, 70, 442-449.  
  18717565 J.P.Ellis, C.K.Bakke, R.N.Kirchdoerfer, L.M.Jungbauer, and S.Cavagnero (2008).
Chain dynamics of nascent polypeptides emerging from the ribosome.
  ACS Chem Biol, 3, 555-566.  
18829863 K.Peisker, D.Braun, T.Wölfle, J.Hentschel, U.Fünfschilling, G.Fischer, A.Sickmann, and S.Rospert (2008).
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.  
18400172 M.Selmer, and A.Liljas (2008).
Exit biology: battle for the nascent chain.
  Structure, 16, 498-500.  
18288106 R.Bingel-Erlenmeyer, R.Kohler, G.Kramer, A.Sandikci, S.Antolić, T.Maier, C.Schaffitzel, B.Wiedmann, B.Bukau, and N.Ban (2008).
A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing.
  Nature, 452, 108-111.
PDB codes: 2vhm 2vhn 2vho 2vhp
18456666 S.Wagner, O.Pop, G.J.Haan, L.Baars, G.Koningstein, M.M.Klepsch, P.Genevaux, J.Luirink, and Gier (2008).
Biogenesis of MalF and the MalFGK(2) maltose transport complex in Escherichia coli requires YidC.
  J Biol Chem, 283, 17881-17890.  
18292779 T.A.Steitz (2008).
A structural understanding of the dynamic ribosome machine.
  Nat Rev Mol Cell Biol, 9, 242-253.  
18043871 Y.Yao, G.Bhabha, G.Kroon, M.Landes, and H.J.Dyson (2008).
Structure discrimination for the C-terminal domain of Escherichia coli trigger factor in solution.
  J Biomol NMR, 40, 23-30.  
17584789 C.L.Ross, R.R.Patel, T.C.Mendelson, and V.C.Ware (2007).
Functional conservation between structurally diverse ribosomal proteins from Drosophila melanogaster and Saccharomyces cerevisiae: fly L23a can substitute for yeast L25 in ribosome assembly and function.
  Nucleic Acids Res, 35, 4503-4514.  
17372359 E.Martinez-Hackert, and W.A.Hendrickson (2007).
Structures of and interactions between domains of trigger factor from Thermotoga maritima.
  Acta Crystallogr D Biol Crystallogr, 63, 536-547.
PDB codes: 2nsa 2nsb 2nsc
18158904 J.F.Ménétret, J.Schaletzky, W.M.Clemons, A.R.Osborne, S.S.Skånland, C.Denison, S.P.Gygi, D.S.Kirkpatrick, E.Park, S.J.Ludtke, T.A.Rapoport, and C.W.Akey (2007).
Ribosome binding of a single copy of the SecY complex: implications for protein translocation.
  Mol Cell, 28, 1083-1092.
PDB codes: 3bo0 3bo1
17804668 M.Kaczanowska, and M.Rydén-Aulin (2007).
Ribosome biogenesis and the translation process in Escherichia coli.
  Microbiol Mol Biol Rev, 71, 477-494.  
17499047 N.Elad, G.W.Farr, D.K.Clare, E.V.Orlova, A.L.Horwich, and H.R.Saibil (2007).
Topologies of a substrate protein bound to the chaperonin GroEL.
  Mol Cell, 26, 415-426.  
17296610 S.K.Lakshmipathy, S.Tomic, C.M.Kaiser, H.C.Chang, P.Genevaux, C.Georgopoulos, J.M.Barral, A.E.Johnson, F.U.Hartl, and S.A.Etchells (2007).
Identification of nascent chain interaction sites on trigger factor.
  J Biol Chem, 282, 12186-12193.  
17525465 Y.Shi, D.J.Fan, S.X.Li, H.J.Zhang, S.Perrett, and J.M.Zhou (2007).
Identification of a potential hydrophobic peptide binding site in the C-terminal arm of trigger factor.
  Protein Sci, 16, 1165-1175.  
16407311 A.Hoffmann, F.Merz, A.Rutkowska, B.Zachmann-Brand, E.Deuerling, and B.Bukau (2006).
Trigger factor forms a protective shield for nascent polypeptides at the ribosome.
  J Biol Chem, 281, 6539-6545.  
16829677 A.Raine, M.Lovmar, J.Wikberg, and M.Ehrenberg (2006).
Trigger factor binding to ribosomes with nascent peptide chains of varying lengths and sequences.
  J Biol Chem, 281, 28033-28038.  
17122845 A.Yonath (2006).
Molecular biology: triggering positive competition.
  Nature, 444, 435-436.  
16754671 B.W.Ying, H.Taguchi, and T.Ueda (2006).
Co-translational binding of GroEL to nascent polypeptides is followed by post-translational encapsulation by GroES to mediate protein folding.
  J Biol Chem, 281, 21813-21819.  
17051157 C.M.Kaiser, H.C.Chang, V.R.Agashe, S.K.Lakshmipathy, S.A.Etchells, M.Hayer-Hartl, F.U.Hartl, and J.M.Barral (2006).
Real-time observation of trigger factor function on translating ribosomes.
  Nature, 444, 455-460.  
17086205 C.Schaffitzel, M.Oswald, I.Berger, T.Ishikawa, J.P.Abrahams, H.K.Koerten, R.I.Koning, and N.Ban (2006).
Structure of the E. coli signal recognition particle bound to a translating ribosome.
  Nature, 444, 503-506.
PDB code: 2iy3
16317791 D.W.Heinz, M.S.Weiss, and K.U.Wendt (2006).
Biomacromolecular interactions, assemblies and machines: a structural view.
  Chembiochem, 7, 203-208.  
16481320 E.van Bloois, G.J.Haan, Gier, B.Oudega, and J.Luirink (2006).
Distinct requirements for translocation of the N-tail and C-tail of the Escherichia coli inner membrane protein CyoA.
  J Biol Chem, 281, 10002-10009.  
16926148 F.Merz, A.Hoffmann, A.Rutkowska, B.Zachmann-Brand, B.Bukau, and E.Deuerling (2006).
The C-terminal domain of Escherichia coli trigger factor represents the central module of its chaperone activity.
  J Biol Chem, 281, 31963-31971.  
16421097 G.Eisner, M.Moser, U.Schäfer, K.Beck, and M.Müller (2006).
Alternate recruitment of signal recognition particle and trigger factor to the signal sequence of a growing nascent polypeptide.
  J Biol Chem, 281, 7172-7179.  
16528757 L.M.Contreras Martínez, F.J.Martínez-Veracoechea, P.Pohkarel, A.D.Stroock, F.A.Escobedo, and M.P.DeLisa (2006).
Protein translocation through a tunnel induces changes in folding kinetics: a lattice model study.
  Biotechnol Bioeng, 94, 105-117.  
16309705 N.Kurt, S.Rajagopalan, and S.Cavagnero (2006).
Effect of hsp70 chaperone on the folding and misfolding of polypeptides modeling an elongating protein chain.
  J Mol Biol, 355, 809-820.  
17021621 P.C.Stirling, S.F.Bakhoum, A.B.Feigl, and M.R.Leroux (2006).
Convergent evolution of clamp-like binding sites in diverse chaperones.
  Nat Struct Mol Biol, 13, 865-870.  
16316984 R.D.Wegrzyn, D.Hofmann, F.Merz, R.Nikolay, T.Rauch, C.Graf, and E.Deuerling (2006).
A conserved motif is prerequisite for the interaction of NAC with ribosomal protein L23 and nascent chains.
  J Biol Chem, 281, 2847-2857.  
16551615 R.S.Ullers, E.N.Houben, J.Brunner, B.Oudega, N.Harms, and J.Luirink (2006).
Sequence-specific interactions of nascent Escherichia coli polypeptides with trigger factor and signal recognition particle.
  J Biol Chem, 281, 13999-14005.  
16239928 S.Grallath, J.P.Schwarz, U.M.Böttcher, A.Bracher, F.U.Hartl, and K.Siegers (2006).
L25 functions as a conserved ribosomal docking site shared by nascent chain-associated complex and signal-recognition particle.
  EMBO Rep, 7, 78-84.  
16413483 V.Albanèse, A.Y.Yam, J.Baughman, C.Parnot, and J.Frydman (2006).
Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells.
  Cell, 124, 75-88.  
15933729 B.Bukau (2005).
Ribosomes catch Hsp70s.
  Nat Struct Mol Biol, 12, 472-473.  
15632130 C.P.Liu, S.Perrett, and J.M.Zhou (2005).
Dimeric trigger factor stably binds folding-competent intermediates and cooperates with the DnaK-DnaJ-GrpE chaperone system to allow refolding.
  J Biol Chem, 280, 13315-13320.  
16091460 D.Baram, E.Pyetan, A.Sittner, T.Auerbach-Nevo, A.Bashan, and A.Yonath (2005).
Structure of trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action.
  Proc Natl Acad Sci U S A, 102, 12017-12022.
PDB code: 2aar
16336118 D.N.Wilson, J.M.Harms, K.H.Nierhaus, F.Schlünzen, and P.Fucini (2005).
Species-specific antibiotic-ribosome interactions: implications for drug development.
  Biol Chem, 386, 1239-1252.  
16257826 D.N.Wilson, and K.H.Nierhaus (2005).
Ribosomal proteins in the spotlight.
  Crit Rev Biochem Mol Biol, 40, 243-267.  
15983062 E.N.Houben, R.Zarivach, B.Oudega, and J.Luirink (2005).
Early encounters of a nascent membrane protein: specificity and timing of contacts inside and outside the ribosome.
  J Cell Biol, 170, 27-35.  
16271892 F.Schlünzen, D.N.Wilson, P.Tian, J.M.Harms, S.J.McInnes, H.A.Hansen, R.Albrecht, J.Buerger, S.M.Wilbanks, and P.Fucini (2005).
The binding mode of the trigger factor on the ribosome: implications for protein folding and SRP interaction.
  Structure, 13, 1685-1694.
PDB code: 2d3o
16156784 G.Zanen, E.N.Houben, R.Meima, H.Tjalsma, J.D.Jongbloed, H.Westers, B.Oudega, J.Luirink, J.M.van Dijl, and W.J.Quax (2005).
Signal peptide hydrophobicity is critical for early stages in protein export by Bacillus subtilis.
  FEBS J, 272, 4617-4630.  
16141058 H.F.Noller (2005).
RNA structure: reading the ribosome.
  Science, 309, 1508-1514.  
16271881 J.H.Cate (2005).
The ins and outs of protein synthesis.
  Structure, 13, 1584-1585.  
16153172 J.Luirink, G.von Heijne, E.Houben, and Gier (2005).
Biogenesis of inner membrane proteins in Escherichia coli.
  Annu Rev Microbiol, 59, 329-355.  
16261170 J.Poehlsgaard, and S.Douthwaite (2005).
The bacterial ribosome as a target for antibiotics.
  Nat Rev Microbiol, 3, 870-881.  
15978066 K.Ito (2005).
Ribosome-based protein folding systems are structurally divergent but functionally universal across biological kingdoms.
  Mol Microbiol, 57, 313-317.  
16244660 M.Blau, S.Mullapudi, T.Becker, J.Dudek, R.Zimmermann, P.A.Penczek, and R.Beckmann (2005).
ERj1p uses a universal ribosomal adaptor site to coordinate the 80S ribosome at the membrane.
  Nat Struct Mol Biol, 12, 1015-1016.  
15701785 O.Vallon (2005).
Chlamydomonas immunophilins and parvulins: survey and critical assessment of gene models.
  Eukaryot Cell, 4, 230-241.  
15821981 P.Giavalisco, D.Wilson, T.Kreitler, H.Lehrach, J.Klose, J.Gobom, and P.Fucini (2005).
High heterogeneity within the ribosomal proteins of the Arabidopsis thaliana 80S ribosome.
  Plant Mol Biol, 57, 577-591.  
16038407 S.P.Place, and G.E.Hofmann (2005).
Temperature differentially affects adenosine triphosphatase activity in Hsc70 orthologs from Antarctic and New Zealand notothenioid fishes.
  Cell Stress Chaperones, 10, 104-113.  
15784745 T.Henrichs, N.Mikhaleva, C.Conz, E.Deuerling, D.Boyd, A.Zelazny, E.Bibi, N.Ban, and M.Ehrmann (2005).
Target-directed proteolysis at the ribosome.
  Proc Natl Acad Sci U S A, 102, 4246-4251.  
15978070 T.Rauch, H.A.Hundley, C.Pfund, R.D.Wegrzyn, W.Walter, G.Kramer, S.Y.Kim, E.A.Craig, and E.Deuerling (2005).
Dissecting functional similarities of ribosome-associated chaperones from Saccharomyces cerevisiae and Escherichia coli.
  Mol Microbiol, 57, 357-365.  
16204885 U.Schulze-Gahmen, S.Aono, S.Chen, H.Yokota, R.Kim, and S.H.Kim (2005).
Structure of the hypothetical Mycoplasma protein MPN555 suggests a chaperone function.
  Acta Crystallogr D Biol Crystallogr, 61, 1343-1347.
PDB code: 1zxj
16204545 Y.Xu, C.L.Weng, N.Narayanan, M.Y.Hsieh, W.A.Anderson, J.M.Scharer, M.Moo-Young, and C.P.Chou (2005).
Chaperone-mediated folding and maturation of the penicillin acylase precursor in the cytoplasm of Escherichia coli.
  Appl Environ Microbiol, 71, 6247-6253.  
15457244 A.Horwich (2004).
Cell biology: sight at the end of the tunnel.
  Nature, 431, 520-522.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.