Trends in Biochemical Sciences
ReviewAtomic structures of the eukaryotic ribosome
Section snippets
General aspects of protein synthesis
In all kingdoms of life, ribosomes are responsible for protein synthesis. These ribonucleoprotein particles have a molecular weight of approximately 2.5 MDa in prokaryotes and contain two subunits with distinct functions. Information encoded in mRNA is decoded by the small subunit (30S), whereas peptide bond formation is catalyzed by the large subunit (50S). In prokaryotes the small subunit is composed of one rRNA (16S) and 20 proteins, whereas the large subunit contains two rRNAs (5S and 23S)
Eukaryotic ribosomes
With a molecular weight of at least 3.3 MDa (yeast), eukaryotic ribosomes are approximately 30% larger than their bacterial counterparts. The small (40S) and the large (60S) ribosomal subunits together form the 80S ribosome. Protein and rRNA components contain long eukaryote-specific extensions and several of the proteins are exclusively present in eukaryotes. Despite largely similar mechanisms of translation, there are several important differences between bacterial and eukaryotic ribosomes.
Eukaryote-specific features of the ribosome
As observed in earlier electron microscopy studies, the eukaryotic 40S and 60S ribosomal subunits share general structural features with their prokaryotic counterparts (30S and 50S respectively) [32]. The 40S subunit can be divided into head, beak, platform, body, shoulder, left foot, and right foot regions (Figure 1a–d). Similarly, the crown view of the 60S subunit shows that the core of the 60S subunit corresponds well to the 50S subunit and key landmarks are conserved, including the central
40S and 60S rRNA structures
In comparison to the bacterial 16S rRNA (∼1500 nucleotides), the eukaryotic 18S rRNA (∼1750 nucleotides) of the 40S subunit contains several expansion segments, which interlink to form the remodeled left foot region (Figure 2a). In particular, ES6, the largest expansion segment of the 18S rRNA, is composed of five substructures (termed ES6A–E), which together with ES3A and ES3B create an interlinked structure. The loop of ES6E interacts with ES3B, thus making an extended helical structure,
40S and 60S ribosomal protein structures
The structure of the 40S subunit in complex with eIF1 highlights the position of all 33 ribosomal proteins of this subunit (Figure 2c,e) [29]. All proteins unique to eukaryotes (rpS7, rpS10, rpS12 and RACK1), and numerous eukaryote-specific extensions of proteins, are located on the solvent-exposed side of the subunit 23, 29. Here, rpS7 has a key architectural function, because it is positioned at the junction from which all substructures of ES6 emanate. An additional example of rRNA–protein
Novel architectural features of the eukaryotic ribosome
A principle emerging from the 40S structure is that the eukaryotic ribosome is stabilized by tertiary contacts, which are mediated by eukaryote-specific ribosomal proteins. Most eukaryote-specific proteins and extensions function to interconnect other proteins of the 40S subunit. In this regard rpS10, rpS12, rpS21 and rpS7 of the 40S subunit are responsible for linking 11 proteins, which connect the head with the body in a ‘daisy-chain’-like manner (Figure 3a,b).
In the eukaryotic 60S subunit,
Functional implications of eukaryotic ribosome structures
The structure of the eukaryotic ribosome facilitates research on the initiation and regulation of eukaryotic translation as well as eukaryotic ribosome maturation.
The crystal structure of the T. thermophila 40S subunit was determined in complex with eIF1; the T. thermophila 60S subunit in complex with eIF6; and the yeast 80S ribosome in complex with Stm1. These complexes have provided the first detailed structural insights into the interactions between regulatory factors involved in initiation
Concluding remarks
During the past 2 years, crystal structures of eukaryotic ribosomal complexes have, for the first time, provided the complete description of the eukaryotic ribosome. At this stage, several key themes are emerging. Extensive structural additions significantly change the molecular structure of the eukaryotic ribosome (Figure 1). Eukaryotic rRNA expansion segments adopt complex folds, which can be used as scaffolds for binding of eukaryote-specific proteins in both subunits (Figure 2). In addition
Acknowledgments
The authors would like to acknowledge support by the Swiss National Science Foundation (SNSF), the National Center of Competence in Research (NCCR) Structural Biology program of the SNSF, and European Research Council grant 250071 under the European Community's Seventh Framework Programme (N.B.) and by EMBO and Human Frontier Science Program postdoctoral fellowships (S.K.).
References (65)
Ribosome structure and the mechanism of translation
Cell
(2002)The termination of translation
Curr. Opin. Struct. Biol.
(2008)Molecular recognition and catalysis in translation termination complexes
Trends Biochem. Sci.
(2011)The eukaryotic ribosome: current status and challenges
J. Biol. Chem.
(2009)- et al.
Maturation of eukaryotic ribosomes: acquisition of functionality
Trends Biochem. Sci.
(2010) - et al.
Deconstructing ribosome construction
Trends Biochem. Sci.
(2009) Driving ribosome assembly
BBA - Mol. Cell Res.
(2010)- et al.
Molecular view of 43 S complex formation and start site selection in eukaryotic translation initiation
J. Biol. Chem.
(2010) - et al.
Recent mechanistic insights into eukaryotic ribosomes
Curr. Opin. Cell Biol.
(2009) Structure–function insights into prokaryotic and eukaryotic translation initiation
Curr. Opin. Struct. Biol.
(2009)
Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide
Mol. Cell
Structure of the mammalian 80S ribosome at 8.7 Å resolution
Structure
Comprehensive molecular structure of the eukaryotic ribosome
Structure
Structure of the 80S ribosome from Saccharomyces cerevisiae—tRNA–ribosome and subunit-subunit interactions
Cell
Ribosomal protein S6 kinase from TOP mRNAs to cell size
Prog. Mol. Biol. Transl. Sci.
Functional interaction in establishment of ribosomal integrity between small subunit protein rpS6 and translational regulator rpL10/Grc5p
FEMS Yeast Res.
Mechanism of eIF6-mediated inhibition of ribosomal subunit joining
J. Biol. Chem.
The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome
Mol. Cell
A snapshot of the 30S ribosomal subunit capturing mRNA via the Shine–Dalgarno interaction
Structure
Toward a structural understanding of IRES RNA function
Curr. Opin. Struct. Biol.
Viral IRES RNA structures and ribosome interactions
Trends Biochem. Sci.
Bridging IRES elements in mRNAs to the eukaryotic translation apparatus
Biochim. Biophys. Acta
Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes
Cell
Inside the 40S ribosome assembly machinery
Curr. Opin. Chem. Biol.
Nuclear export and cytoplasmic maturation of ribosomal subunits
FEBS Lett.
Pre-ribosomes on the road from the nucleolus to the cytoplasm
Trends Cell Biol.
Mechanochemical removal of ribosome biogenesis factors from nascent 60S ribosomal subunits
Cell
Defining the pathway of cytoplasmic maturation of the 60S ribosomal subunit
Mol. Cell
PSRP1 is not a ribosomal protein, but a ribosome-binding factor that is recycled by the ribosome-recycling factor (RRF) and elongation factor G (EF-G)
J. Biol. Chem.
What recent ribosome structures have revealed about the mechanism of translation
Nature
Ribosome dynamics: insights from atomic structure modeling into cryo-electron microscopy maps
Annu. Rev. Biophys. Biomol. Struct.
A structural view of translation initiation in bacteria
Cell. Mol. Life Sci.
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