Crystal Structure of the Eukaryotic Ribosome

Ben-Shem, Adam; Jenner, L.; Yusupova, G.; Yusupov, Marat

doi:10.1126/science.1194294

Cited by 378 publications

(416 citation statements)

References 41 publications

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“…One site of major expansion is the CP, which because of its location is thought to facilitate communication between various functional sites of the ribosome in a manner that is not fully understood (30,31). In bacterial, archaeal and eukaryotic ribosomes, the CP consists of a separate 5S rRNA core interacting with several ribosomal proteins and 23S rRNA.…”

Section: The Central Protuberance (Cp)mentioning

confidence: 99%

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

et al. 2014

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# These authors contributed equally to this work. AbstractMitochondria have specialized ribosomes that have diverged from their bacterial and cytoplasmic counterparts. We have solved the structure of the yeast mitoribosomal large subunit using singleparticle electron cryo-microscopy. The resolution of 3.2 Ångstroms enabled a nearly complete atomic model to be built de novo and refined, including 39 proteins, 13 of which are unique to mitochondria, as well as expansion segments of mitoribosomal RNA. The structure reveals a new exit tunnel path and architecture, unique elements of the E site and a putative membrane docking site.Mitochondria are organelles in eukaryotic cells that play a major role in metabolism, especially the synthesis of ATP. During evolution, mitochondria have lost or transferred most of their genes to the nuclei, significantly reducing the size of their genome (1). In yeast, all but one of the few remaining protein genes encode subunits of respiratory chain complexes, whose synthesis involves insertion into the inner mitochondrial membrane along with incorporation of prosthetic groups (2). For the translation of these genes, mitochondria maintain their own ribosomes (mitoribosomes) and translation system. The mitochondrial ribosomal RNA and several tRNAs are encoded by the mitochondrial genome, whereas all but one of its ribosomal proteins are nuclear encoded and imported from the cytoplasm. Mitoribosomes have diverged greatly from their counterparts in the cytosol of bacterial and eukaryotic cells and also exhibit high variability depending on species (Table S1) (3). Several genetic diseases map to mitoribosomes (4). In addition, the toxicity of many ribosomal antibiotics, in particular aminoglycosides, is thought to be due to their interaction with the mitoribosome (5).Mitochondrial translation in the yeast Saccharomyces cerevisiae (6) has been used as a model to study human mitochondrial diseases (7). The 74S yeast mitoribosome has an overall molecular weight of 3 MDa, or 30% higher than that of their bacterial counterpart. It consists of a 54S large subunit (1.9 MDa) and a 37S small subunit (1.1 MDa). Highresolution crystal structures have been solved for bacterial (8, 9) and eukaryotic ribosomes (10-12), as well as for an archaeal large subunit (13). In comparison, the only structures to † To whom correspondence should be addressed at scheres@mrc-lmb.cam.ac.uk or ramak@mrc-lmb.cam.ac.uk. Europe PMC Funders Group Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts date for mitoribosomes come from electron cryo-microscopy (cryo-EM) reconstructions at 12-14 Å (14-16).The very low yields of mitoribosomes from most tissues have impeded their crystallization. However, the advent of high-speed direct electron detectors (that allow accounting for particle movement during imaging) (17, 18), and improved algorithms for the classification and alignment of particles (19), allowed us to determine the structure of the large subunit of the yeast mitoribosome (hereafter referred t...

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Section: The Central Protuberance (Cp)mentioning

confidence: 99%

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

et al. 2014

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“…1,2 Eukaryotic 80S ribosomes (composed of 60S and 40S subunits) have evolved to be much larger in size with more proteins and ribosomal RNA (rRNA) than their archeal, or bacterial counterparts, (70S ribosomes composed of 50S and 30S subunits). [3][4][5][6] Recent X-ray crystal structures of the yeast 80S ribosome at 3.0 A resolution permitted detailed analysis of the structural organization of the eukaryotic ribosome. 5,6 It became evident that bacterial and eukaryotic ribosomes evolved from a common structural (RNP) core with the majority of changes occurring on the outer shell of the ribosome.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6] Recent X-ray crystal structures of the yeast 80S ribosome at 3.0 A resolution permitted detailed analysis of the structural organization of the eukaryotic ribosome. 5,6 It became evident that bacterial and eukaryotic ribosomes evolved from a common structural (RNP) core with the majority of changes occurring on the outer shell of the ribosome. These changes include extra rRNA (expansion segments) and additional ribosomal proteins enveloping the core on the solvent side of the ribosome.…”

Section: Introductionmentioning

confidence: 99%

“…The 80S yeast ribosome contains 79 proteins, of which 46 are eukaryotespecific (18 in the 40S subunit and 28 in the 60S subunit). 5,6 Thirty four proteins (15 in the 40S subunit and 19 in the 60S subunit) are conserved across all kingdoms of life. 5 Interestingly, despite general similarity in sequence and structure, many of the conserved ribosomal proteins have evolved eukaryote-specific extensions, the functional significance of which is largely unknown and/or just beginning to emerge.…”

Section: Introductionmentioning

confidence: 99%

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Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

Ghosh

Komar

2015

Translation

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Keywords: conserved ribosomal proteins, eukaryotic/yeast ribosome, eukaryote-specific extensions, eukaryotic translation initiation factors, protein synthesis, small ribosomal subunitHigh-resolution structures of yeast ribosomes have improved our understanding of the architecture and organization of eukaryotic rRNA and proteins, as well as eukaryote-specific extensions present in some conserved ribosomal proteins. Despite this progress, assignment of specific functions to individual proteins and/or eukaryotespecific protein extensions remains challenging. It has been suggested that eukaryote-specific extensions of conserved proteins from the small ribosomal subunit may facilitate eukaryote-specific reactions in the initiation phase of protein synthesis. This review summarizes emerging data describing the structural and functional significance of eukaryotespecific extensions of conserved small ribosomal subunit proteins, particularly their possible roles in recruitment and spatial organization of eukaryote-specific initiation factors.

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“…The largest expansion segment in small 18S rRNA is ES6S, which is about 200 nucleotides in length. The secondary structure of ES6S cannot be determined using a co-variance model without phylogenetic data ( Figure S5 in Supporting Information), but two long helices in ES6S can be derived from crystal structures [23,43] (Figure 3B). In the crystal structure, these ES6S helices are exposed on the ribosome surface [40].…”

Section: Rbp Binding Facilitates Rna Secondary Structure Conformationmentioning

confidence: 99%

Global signatures of protein binding on structured RNAs in Saccharomyces cerevisiae

Yang

Umetsu

2013

Sci. China Life Sci.

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Protein binding is essential to the transport, decay and regulation of almost all RNA molecules. However, the structural preference of protein binding on RNAs and their cellular functions and dynamics upon changing environmental conditions are poorly understood. Here, we integrated various high-throughput data and introduced a computational framework to describe the global interactions between RNA binding proteins (RBPs) and structured RNAs in yeast at single-nucleotide resolution. We found that on average, in terms of percent total lengths, ~15% of mRNA untranslated regions (UTRs), ~37% of canonical non-coding RNAs (ncRNAs) and ~11% of long ncRNAs (lncRNAs) are bound by proteins. The RBP binding sites, in general, tend to occur at single-stranded loops, with evolutionarily conserved signatures, and often facilitate a specific RNA structure conformation in vivo. We found that four nucleotide modifications of tRNA are significantly associated with RBP binding. We also identified various structural motifs bound by RBPs in the UTRs of mRNAs, associated with localization, degradation and stress responses. Moreover, we identified >200 novel lncRNAs bound by RBPs, and about half of them contain conserved secondary structures. We present the first ensemble pattern of RBP binding sites in the structured non-coding regions of a eukaryotic genome, emphasizing their structural context and cellular functions. . Many mRNAs are regulated by one or more RBPs as co-regulators. In Saccharomyces cerevisiae, there are approximately 600 annotated and predicted RBPs, but relatively few of them have been systematically studied to determine their regulatory targets [5]. In addition to mRNAs, numerous non-coding RNAs (ncRNAs) are targets of RBPs [6,7]. Previous studies revealed that RNAs were regulated by many RBPs post-transcriptionally [8]. It is widely accepted that altering the expression of RBPs will change cellular physiology profoundly. Studies using animal models have revealed that RBPs are involved in many human diseases, such as neurologic disorders and cancers [9]. Although the mechanisms that confer the specificity of RBP-RNA interaction are poorly understood, it is clear that this specificity is determined by both the primary sequence and secondary structure of the target RNA [10,11]. The secondary structures recognized by some RBPs are known. For example, the SAM domain of the yeast post-transcriptional regulator Vts1p recognizes the shape of the SRE of the RNA ligand [12].Currently, the most direct and powerful approach to profiling RBP-RNA interactions is UV crosslinking and immunoprecipitation (CLIP) of RNA-protein complexes,

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Crystal Structure of the Eukaryotic Ribosome

Cited by 378 publications

References 41 publications

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

Global signatures of protein binding on structured RNAs in Saccharomyces cerevisiae

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