Ribosomal Proteins: Role in Ribosomal Functions

Daniel N Wilson, University of Munich, Munich, Germany
Romi Gupta, Max‐Planck Institute for Molecular Genetics, Berlin, Germany
Aleksandra Mikolajka, University of Munich, Munich, Germany
Knud H Nierhaus, Max‐Planck Institute for Molecular Genetics, Berlin, Germany

Published online: September 2009

DOI: 10.1002/9780470015902.a0000687.pub3

Full Article on Wiley Online Library

The assignment of specific ribosomal functions to individual ribosomal proteins is difficult due to the enormous cooperativity of the ribosome; however, important roles for distinct ribosomal proteins are becoming evident. Although ribosomal ribonucleic acid (rRNA) has the major claim to certain aspects of ribosome function, such as decoding and peptidyltransferase activity, there are also protein-dominated functional hot-spots on the ribosome such as the messenger RNA (mRNA) entry pore, the translation factor-binding site and the exit of the ribosomal tunnel. The latter is binding site for both chaperones and complexes associated with protein transport through membranes. Furthermore, the contribution of ribosomal proteins is essential for the assembly and optimal functioning of the ribosome.

Key concepts:

Both the 16S and 23S rRNAs and a subset of r-proteins are essential for assembly, structure and function of ribosomes; the ribosomal interface, the place where the three tRNA-binding sites A, P and E are located and thus where protein synthesis occurs, is preferentially composed of rRNA; functional hot-spots such as mRNA entry pore, elongation factor-binding site (L7/L12 stalk), the L1 protuberance and the tunnel exit are dominated by r-proteins; many r-proteins have a globular domain and long extensions protruding deep into the ribosome; the globular domains of r-proteins are located at or near the ribosomal surface; antibiotic resistance can be mediated by mutations in either rRNA or r-protein genes; some r-proteins are essential for assembly but play no role in structure or function of the ribosome; accuracy of proteins is tuned and balanced by r-proteins (S4, S5 and S12); r-proteins at the tunnel exit can function as a docking station for factors important for protein folding or for attaching the ribosome to membranes.

Keywords: rRNA-binding proteins; translational regulation; antitermination; antibiotic resistance; mutant proteins; binding of translational factors

	Figure 1. Position of ribosomal proteins in the T. thermophilus 30S subunit. (a) Domain distribution of r-proteins (dark) and rRNA (light) in the 30S subunit with colouring coded by domain: 5¢ domain, blue (body); central domain, purple (platform); 3¢ major, green (head) and 3¢ minor, yellow (h44 and h45). (b) Spacefill representation of 30S subunit highlighting positions of r-proteins S4 (cyan), S5 (red), S7 (green), S11 (pink) and S12 (purple), whereas other r-proteins and rRNA coloured blue and yellow, respectively. Both interface (which contacts 50S subunit) and solvent (cytoplasmic) views are shown.
	Figure 2. The flexibility of the L1 stalk. The more open position of the L1 stalk in the D. radiodurans 50S subunit (blue) compared with that present in the T. thermophilus 70S ribosome (tan) suggests that opening and closing of the L1 stalk may regulate release of the E site tRNA (orange). The P site tRNA is shown in purple.
	Figure 3. Involvement of S4, S5 and S12 during decoding. (a) Binding of cognate tRNA to the A site induces a transition in the 30S subunit from the open to the closed form. This involves a rotation of the head and movement of body (see arrows) towards the decoding site (anticodon–stem loop (ASL) of tRNA indicated (green) to indicate A site position). The closed-form brings elements of S12 (grey) and h44 (orange) into contact. (b) Serine 46 (Ser46) in the loop of S12 monitors the correctness of the second position base pair of the A site codon–anticodon complex (U1 in the mRNA-A35 in the tRNA) by hydrogen bonding with A1492 of the 16S rRNA. (c) Ram mutations shown in orange and purple spacefill representation that disrupt the interface between r-proteins S4 (cyan) and S5 (blue) facilitate transition from the open to the closed form.
	Figure 4. Ribosomal proteins located in the ribosomal tunnel and at the exit site. (a) Sideview (from L1 side) of 50S subunit highlighting r-proteins L4, L22 and L23, the extensions of which reach into the tunnel (indicated by theoretical nascent polypeptide chain in yellow). (b) Close-up of the ribosomal components at the tunnel kink, located adjacent to the PTF centre indicated with A- (red) and P site (blue) ligands. The extensions of r-proteins L4 (orange) and L22 (green) reach into the interior of the ribosome but do not come into contact with the macrolide erythromycin (ery) despite the fact that mutations (K63E in L4) or deletions (₈₂MEK₈₄ in L22) in these proteins confer resistance to this drug. Relief of the translational arrest caused by SecM resulting from mutation at positions Gly91 and Ala93 in L22 (space filled in light green) and five nucleotide insertion at position A749 of the 23S rRNA. Mutations at position A2058 (purple) of the 23S rRNA confer resistance to erythromycin and relieve SecM translational arrest. The path of a hypothetical SecM nascent chain is shown with Pro (P) at the active site and Trp/Ile (WI) located in vicinity of the -hairpin of L22. (c) View onto the tunnel exit from cytoplasmic side of 50S subunit showing the positions of the r-proteins located at the exit site (white arrow). (d) The trigger factor (purple) with head, body and tail interacts via the latter with r-protein L23 at the exit site of the tunnel. The full-length TF crystal structure has been docked on to the D50S subunit on the basis of the binding position of the N-terminal-binding domain (according to Schluenzen et al., 2005).

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Further Reading
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	Wilson DN and Nierhaus KH (2003) The ribosome through the looking glass. Angewandte Chemie International Edition 43: 3463–3486.
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	Wittmann H-G (1982) Components of bacterial ribosomes. Annual Review of Biochemistry 51: 155–183.
	book Wittmann-Liebold B, Köpke AKE, Arndt E et al. (1990) "Sequence comparison and evolution of ribosomal proteins and their genes". In: Hill WE, Dahlberg A, Garrett RA et al. (eds) The Ribosome: Structure, Function and Evolution. Washington DC: American Society for Microbiology.

Article Title:	Ribosomal Proteins: Role in Ribosomal Functions
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