Proteins at the Polypeptide Tunnel Exit of the Yeast Mitochondrial Ribosome

Gruschke, Steffi; Gröne, Kerstin; Heublein, Manfred; Hölz, Stefanie; Israel, Lars; Imhof, Axel; Herrmann, Johannes M.; Ott, Martin

doi:10.1074/jbc.m110.113837

Cited by 63 publications

(66 citation statements)

References 23 publications

(37 reference statements)

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“…This suggests that the attachment to a translocon-like entity for insertion of the nascent peptide into t he mitochondrial membrane must be very different in the 54S compared to bacterial ribosomes. In support of this idea, uL23, uL24, mL44 and mL50 were chemically found to cross-link with each other (36). The exit of the tunnel is also wider than in bacteria, possibly to allow co-translational assembly of oxidative phosphorylation complexes (34,37).…”

Section: The Exit Tunnelmentioning

confidence: 66%

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 Exit Tunnelmentioning

confidence: 66%

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

et al. 2014

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“…Homologs of all of these proteins are present in yeast mitochondrial ribosomes. In addition, the region near the exit tunnel of yeast mitochondrial ribosomes contains several mitochondrial specific ribosomal proteins including Mrpl3, Mrpl13, and Mrpl27 (44). Yeast Oxa1p can be cross-linked to mitochondrial ribosomal proteins that are homologs of bacterial L23 (Mrp20) and L24 (MrpL40) at the exit tunnel (6,10).…”

Section: Discussionmentioning

confidence: 99%

Properties of the C-terminal Tail of Human Mitochondrial Inner Membrane Protein Oxa1L and Its Interactions with Mammalian Mitochondrial Ribosomes

Haque

Elmore

Tripathy

et al. 2010

Journal of Biological Chemistry

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In humans the mitochondrial inner membrane protein Oxa1L is involved in the biogenesis of membrane proteins and facilitates the insertion of both mitochondrial-and nuclear-encoded proteins from the mitochondrial matrix into the inner membrane. The C-terminal ϳ100-amino acid tail of Oxa1L (Oxa1L-CTT) binds to mitochondrial ribosomes and plays a role in the co-translational insertion of mitochondria-synthesized proteins into the inner membrane. Contrary to suggestions made for yeast Oxa1p, our results indicate that the C-terminal tail of human Oxa1L does not form a coiled-coil helical structure in solution. The Oxa1L-CTT exists primarily as a monomer in solution but forms dimers and tetramers at high salt concentrations. The binding of Oxa1L-CTT to mitochondrial ribosomes is an enthalpy-driven process with a K d of 0.3-0.8 M and a stoichiometry of 2. Oxa1L-CTT cross-links to mammalian mitochondrial homologs of the bacterial ribosomal proteins L13, L20, and L28 and to mammalian mitochondrial specific ribosomal proteins MRPL48, MRPL49, and MRPL51. Oxa1L-CTT does not cross-link to proteins decorating the conventional exit tunnel of the bacterial large ribosomal subunit (L22, L23, L24, and L29).

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“…Importantly, the regions around the polypeptide exit tunnel show significant structural variation (20). This is supported by analysis of the composition of the yeast ribosomal exit tunnel that identified proteins that were homologous to the bacterial exit tunnel proteins but contained mitochondrion-specific domains and the N and C termini (18). In addition, three mitochondrion-specific proteins were found to be close to the exit tunnel.…”

Section: Discussionmentioning

confidence: 54%

“…While the RNA/protein ratio for some mitochondrial ribosomes is 1/3, bacterial ribosomes usually have a ratio of 2/1, which corresponds to a much greater RNA content of the bacterial ribosomes (17). Although detailed structural information on mitochondrial ribosomes is limited, cryo-electron microscopy (cryo-EM) and biochemical studies indicate substantial differences in the exit tunnel area of bacterial and mitochondrial ribosomes (18)(19)(20). This part of the ribosome is considered to constitute the YidC binding site, yet which specific characteristics determine the interaction is largely unresolved.…”

mentioning

confidence: 99%

Interaction of Streptococcus mutans YidC1 and YidC2 with Translating and Nontranslating Ribosomes

Keyzer

Berrelkamp-Lahpor

et al. 2013

J Bacteriol

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The YidC/OxaI/Alb3 family of membrane proteins is involved in the biogenesis of integral membrane proteins in bacteria, mitochondria, and chloroplasts. Gram-positive bacteria often contain multiple YidC paralogs that can be subdivided into two major classes, namely, YidC1 and YidC2. The Streptococcus mutans YidC1 and YidC2 proteins possess C-terminal tails that differ in charges (؉9 and ؉ 14) and lengths (33 and 61 amino acids). The longer YidC2 C terminus bears a resemblance to the C-terminal ribosome-binding domain of the mitochondrial OxaI protein and, in contrast to the shorter YidC1 C terminus, can mediate the interaction with mitochondrial ribosomes. These observations have led to the suggestion that YidC1 and YidC2 differ in their abilities to interact with ribosomes. However, the interaction with bacterial translating ribosomes has never been addressed. Here we demonstrate that Escherichia coli ribosomes are able to interact with both YidC1 and YidC2. The interaction is stimulated by the presence of a nascent membrane protein substrate and abolished upon deletion of the C-terminal tail, which also abrogates the YidC-dependent membrane insertion of subunit c of the F 1 F 0 -ATPase into the membrane. It is concluded that both YidC1 and YidC2 interact with ribosomes, suggesting that the modes of membrane insertion by these membrane insertases are similar.

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Proteins at the Polypeptide Tunnel Exit of the Yeast Mitochondrial Ribosome

Cited by 63 publications

References 23 publications

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

Structure of the Yeast Mitochondrial Large Ribosomal Subunit

Properties of the C-terminal Tail of Human Mitochondrial Inner Membrane Protein Oxa1L and Its Interactions with Mammalian Mitochondrial Ribosomes

Interaction of Streptococcus mutans YidC1 and YidC2 with Translating and Nontranslating Ribosomes

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