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Domain 4:

Synthesis and Processing of Macromolecules

An Introduction to the Structure and Function of the Ribosome

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  • Authors: Jack A. Dunkle1, and Jamie H. D. Cate2
  • Editor: Susan T. Lovett3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Molecular and Cell Biology, Berkeley, CA 94720; 2: Department of Molecular and Cell Biology and Department of Chemistry, University of California at Berkeley, and Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; 3: Brandeis University, 415 South Street, Waltham, MA 02453
  • Received 14 June 2012 Accepted 29 August 2012 Published 19 February 2013
  • Address correspondence to Jamie H. D. Cate jcate@lbl.gov
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  • Abstract:

    continues to serve as a key model for the structure and function of the ribosome, structures of ribosome from other organisms and domains of life have also greatly contributed to our knowledge of protein synthesis. Many structural models of the ribosome in a number of steps of the protein synthesis cycle have been solved by cryo-electron microscopy (cryo-EM) and x-ray crystallography. This chapter introduces the structure and dynamics of the ribosome based on these structures and ends with a brief discussion of the many questions that the structures leave unanswered. Protein synthesis is a multistep process, and the structural features of the ribosome along with the large number of cofactors reflect the complexity of translation. Numerous protein factors in addition to the ribosome contribute to translation in bacteria during the steps of initiation, elongation, termination, and recycling. These protein factors make intimate contacts to key regions of the ribosome, and this aspect is discussed in the chapter in light of our present understanding of the structure and function of the ribosome. The intact ribosome contains three binding sites for substrate tRNAs that are termed as the aminoacyl-tRNA site (A site), peptidyl-tRNA site (P site), and exit-tRNA site (E site). These three binding sites span the interface between the 30S and 50S subunits. The central activity of the ribosome is catalysis of peptide bond formation. The region of the ribosome responsible for catalyzing the reaction is called the peptidyl transferase center (PTC).

  • Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2

Key Concept Ranking

Genetic Code
0.34870347
Messenger RNA
0.34666666
Ribosome Binding Site
0.34633955
Ribosomal RNA
0.34276703
0.34870347

References

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29. Yang X, Gerczei T, Glover LT, Correll CC. 2001. Crystal structures of restrictocin-inhibitor complexes with implications for RNA recognition and base flipping. Nat Struct Biol 8:968–973.
30. Komoda T, Sato NS, Phelps SS, Namba N, Joseph S, Suzuki T. 2006. The A-site finger in 23S rRNA acts as a functional attenuator for translocation. J Biol Chem 281:32303–32309.
31. Korostelev A, Ermolenko DN, Noller HF. 2008. Structural dynamics of the ribosome. Curr Opin Chem Biol 12:674–683.
32. Zhang W, Dunkle JA, Cate JH. 2009. Structures of the ribosome in intermediate states of ratcheting. Science 325:1014–1017.
33. Zhou J, Lancaster L, Trakhanov S, Noller HF. 2012. Crystal structure of release factor RF3 trapped in the GTP state on a rotated conformation of the ribosome. RNA 18:230–240.
34. Yusupova GZ, Yusupov MM, Cate JH, Noller HF. 2001. The path of messenger RNA through the ribosome. Cell 106:233–241.
35. Takyar S, Hickerson RP, Noller HF. 2005. mRNA helicase activity of the ribosome. Cell 120:49–58.
36. Borovinskaya MA, Shoji S, Holton JM, Fredrick K, Cate JH. 2007. A steric block in translation caused by the antibiotic spectinomycin. ACS Chem Biol 2:545–552.
37. Nissen P, Hansen J, Ban N, Moore PB, Steitz TA. 2000. The structural basis of ribosome activity in peptide bond synthesis. Science 289:920–930.
38. Schmeing TM, Huang KS, Strobel SA, Steitz TA. 2005. An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Nature 438:520–524.
39. Voorhees RM, Weixlbaumer A, Loakes D, Kelley AC, Ramakrishnan V. 2009. Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome. Nat Struct Mol Biol 16:528–533.
40. Beringer M. 2008. Modulating the activity of the peptidyl transferase center of the ribosome. RNA 14:795–801.
41. Petrone PM, Snow CD, Lucent D, Pande VS. 2008. Side-chain recognition and gating in the ribosome exit tunnel. Proc Natl Acad Sci USA 105:16549–16554.
42. Lill R, Robertson JM, Wintermeyer W. 1989. Binding of the 3′ terminus of tRNA to 23S rRNA in the ribosomal exit site actively promotes translocation. EMBO J 8:3933–3938.
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44. Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH. 2007. Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nat Struct Mol Biol 14:727–732.
45. Borovinskaya MA, Shoji S, Fredrick K, Cate JH. 2008. Structural basis for hygromycin B inhibition of protein biosynthesis. RNA 14:1590–1599.
46. Poehlsgaard J, Douthwaite S. 2005. The bacterial ribosome as a target for antibiotics. Nat Rev Microbiol 3:870–881.
47. Schluenzen F, Takemoto C, Wilson DN, Kaminishi T, Harms JM, Hanawa-Suetsugu K, Szaflarski W, Kawazoe M, Shirouzu M, Nierhaus KH, Yokoyama S, Fucini P. 2006. The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation. Nat Struct Mol Biol 13:871–878.
48. Schuwirth BS, Day JM, Hau CW, Janssen GR, Dahlberg AE, Cate JH, Vila-Sanjurjo A. 2006. Structural analysis of kasugamycin inhibition of translation. Nat Struct Mol Biol 13:879–886.
49. Bulkley D, Innis CA, Blaha G, Steitz TA. 2010. Revisiting the structures of several antibiotics bound to the bacterial ribosome. Proc Natl Acad Sci USA 107:17158–17163.
50. Dunkle JA, Xiong L, Mankin AS, Cate JH. 2010. Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action. Proc Natl Acad Sci USA 107:17152–17157.
51. Harms JM, Wilson DN, Schluenzen F, Connell SR, Stachelhaus T, Zaborowska Z, Spahn CM, Fucini P. 2008. Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin. Mol Cell 30:26–38.
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56. Saini P, Eyler DE, Green R, Dever TE. 2009. Hypusine-containing protein eIF5A promotes translation elongation. Nature 459:118–121.
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2013-02-19
2017-09-22

Abstract:

continues to serve as a key model for the structure and function of the ribosome, structures of ribosome from other organisms and domains of life have also greatly contributed to our knowledge of protein synthesis. Many structural models of the ribosome in a number of steps of the protein synthesis cycle have been solved by cryo-electron microscopy (cryo-EM) and x-ray crystallography. This chapter introduces the structure and dynamics of the ribosome based on these structures and ends with a brief discussion of the many questions that the structures leave unanswered. Protein synthesis is a multistep process, and the structural features of the ribosome along with the large number of cofactors reflect the complexity of translation. Numerous protein factors in addition to the ribosome contribute to translation in bacteria during the steps of initiation, elongation, termination, and recycling. These protein factors make intimate contacts to key regions of the ribosome, and this aspect is discussed in the chapter in light of our present understanding of the structure and function of the ribosome. The intact ribosome contains three binding sites for substrate tRNAs that are termed as the aminoacyl-tRNA site (A site), peptidyl-tRNA site (P site), and exit-tRNA site (E site). These three binding sites span the interface between the 30S and 50S subunits. The central activity of the ribosome is catalysis of peptide bond formation. The region of the ribosome responsible for catalyzing the reaction is called the peptidyl transferase center (PTC).

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Figures

Image of Figure 1
Figure 1

(A) View of the 70S ribosome from the solvent side of the 30S subunit. Structural landmarks are marked: head, body, platform, spur in the 30S subunit; L1 and L11 arms in the 50S subunit. In the 30S subunit, 16S rRNA (light blue) and small subunit (S) proteins (dark blue) are shown. In the 50S subunit, 5S and 23S rRNA (grey) and large subunit (L) proteins (purple) are shown. Because of the inherently dynamic nature of proteins L1 and L7/12, they are not visible in x-ray crystal structures of the ribosome, but can be modeled onto the structure of the 50S subunit, as shown, by superposition of homologous structures ( 8 , 16 ). (B) View of the 70S ribosome from the perspective of the 50S subunit. Labeling is as described in panel A. An additional landmark in the 50S subunit, the central protuberance (CP), is shown. (C) View of the interface between the ribosomal subunits. Contacts or “bridges” to the opposite subunit are labeled and colored red.

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 2
Figure 2

(A) Schematic of the 70S ribosome indicating the positions of the aminoacyl-tRNA, peptidyl-tRNA, and exit-tRNA binding sites (A, P, and E sites, respectively). Additional binding sites for tRNAs occur for initiator-tRNA (I on the 50S subunit), during mRNA decoding (T on the 50S subunit), and during translocation ( 12 , 17 ). (B) View of the structure of the 70S ribosome rotated 90° about the vertical axis in Fig. 1A . The binding sites for A-site tRNA and mRNA are marked, along with the domains of the 30S subunit and the central protuberance (CP) of the 50S subunit. (C) Slice through the 70S ribosome as indicated by icon. Views of the ribosome with tRNAs bound in the A/A, P/P, and E/E sites (30S/50S sites, respectively). The approximate locations of the I and T sites on the 50S subunit are marked. Protein L1, the CP, and the L11 arm are marked.

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 3
Figure 3

(A) Global features of the 30S subunit viewed from the perspective of the interface with the 50S subunit. The three tRNA binding sites are labeled A, P, and E. The anticodon stem-loops of the A-site (yellow), P-site (orange), and E-site (red) tRNAs are shown for perspective. Color coding of the 30S subunit is the same as in Fig. 1 . (B) Close-up of the mRNA decoding site with the nucleotides that read out the mRNA codon/tRNA anticodon helix minor groove indicated. Messenger RNA is in green. (C) View of A-site tRNA in the process of mRNA decoding, as viewed by cryo-EM. The tRNA is in the A/T state at this step of decoding. The GTPase-associated center (GAC) of the ribosome is shown.

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 4
Figure 4

(A) Rotation of the 30S subunit relative to the 50S subunit. The axis of rotation is approximately perpendicular to the page. Coloring of the 30S and 50S subunit RNAs and proteins is as in Fig. 1 . (B) Positioning of tRNAs in hybrid states of binding when the 30S subunit is rotated relative to the 50S subunit. Before subunit rotation, tRNAs occupy the A/A and P/P sites ( Fig. 2C ) and shift into the A/P and P/E sites after subunit rotation. (C) Movement of the 30S subunit head domain during translocation, viewed from the perspective of the 30S subunit interface with the 50S subunit. Proteins S19, S13, and h33 of 16S rRNA are marked.

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 5
Figure 5

A view of interactions made between EF-G and the ribosome is pictured. A model of proteins L7/12 docked onto the 50S using electron density derived from EM maps is shown ( 16 ). Proteins L7/12 are dynamic and are not clearly visible in x-ray crystal structures of the intact ribosome. The Sarcin-Ricin Loop (SRL) (red) is shown contacting the G-domain (green) of EF-G. The GTPase domain of other translation factors likely occupies positions similar to that of EF-G.

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 6
Figure 6

View of the L1 arm in the 50S subunit from the perspective of the 30S subunit. E-site tRNA is shown for reference. The L1 arm is composed of the L1 protein and 23S rRNA helices 76 to 78.

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 7
Figure 7

(A) The region of mRNA 5′ of the tRNA binding sites (green) can base pair with the 3′ end of 16S rRNA (light blue) during initiation. (B) The 3′ region of mRNA (green) following the A-site codon enters through a path surrounded by ribosomal proteins S3 (gold), S4 (red), and S5 (orange).

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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Image of Figure 8
Figure 8

(A) Binding of tRNAs in the P site and A site in the peptidyl transferase center (PTC). tRNAs are pictured charged with an amino acid on the terminal adenosine of each tRNA. Hydrogen bonds between tRNAs and 23S rRNA are shown as black dashes. An arrow indicates the nucleophilic amine group that can attack the ester bond linking the nascent peptide chain to P-site tRNA. (B) Binding pocket in the 50S subunit for the 3′-adenosine of E-site tRNA. Hydrogen bonds between E-site tRNA and 23S rRNA are shown as black dashes. Note that the pocket differs slightly in archaeal and eukaryotic ribosomes ( 8 ).

Citation: Dunkle J, Cate J. 2013. An Introduction to the Structure and Function of the Ribosome, EcoSal Plus 2013; doi:10.1128/ecosal.2.5.2
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