| 1. |
- Amunts, Alexey
(författare)
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The revolution evolution
- 2022
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Ingår i: Nature Plants. - : Springer Science and Business Media LLC. - 2055-0278. ; 8:1, s. 14-17
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Cottilli, Patrick, et al.
(författare)
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Cryo-EM structure and rRNA modification sites of a plant ribosome
- 2022
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Ingår i: Plant Communications. - : Elsevier BV. - 2590-3462. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Protein synthesis in crop plants contributes to the balance of food and fuel on our planet, which influences human metabolic activity and lifespan. Protein synthesis can be regulated with respect to changing environmental cues via the deposition of chemical modifications into rRNA. Here, we present the structure of a plant ribosome from tomato and a quantitative mass spectrometry analysis of its rRNAs. The study reveals fine features of the ribosomal proteins and 71 plant-specific rRNA modifications, and it re-annotates 30 rRNA residues in the available sequence. At the protein level, isoAsp is found in position 137 of uS11, and a zinc finger previously believed to be universal is missing from eL34, suggesting a lower effect of zinc deficiency on protein synthesis in plants. At the rRNA level, the plant ribosome differs markedly from its human counterpart with respect to the spatial distribution of modifications. Thus, it represents an additional layer of gene expression regulation, highlighting the molecular signature of a plant ribosome. The results provide a reference model of a plant ribosome for structural studies and an accurate marker for molecular ecology.
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| 3. |
- Gahura, Ondřej, et al.
(författare)
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An ancestral interaction module promotes oligomerization in divergent mitochondrial ATP synthases
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial ATP synthase forms stable dimers arranged into oligomeric assemblies that generate the inner-membrane curvature essential for efficient energy conversion. Here, we report cryo-EM structures of the intact ATP synthase dimer from Trypanosoma brucei in ten different rotational states. The model consists of 25 subunits, including nine lineage-specific, as well as 36 lipids. The rotary mechanism is influenced by the divergent peripheral stalk, conferring a greater conformational flexibility. Proton transfer in the lumenal half-channel occurs via a chain of five ordered water molecules. The dimerization interface is formed by subunit-g that is critical for interactions but not for the catalytic activity. Although overall dimer architecture varies among eukaryotes, we find that subunit-g together with subunit-e form an ancestral oligomerization motif, which is shared between the trypanosomal and mammalian lineages. Therefore, our data defines the subunit-g/e module as a structural component determining ATP synthase oligomeric assemblies. Mitochondrial ATP synthase assemble into oligomers. Here, authors resolve the structure of trypanosomal ATP synthase, showing that its dimerization is essential for function and evolutionary conserved.
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| 4. |
- Itoh, Yuzuru, et al.
(författare)
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Mechanism of mitoribosomal small subunit biogenesis and preinitiation
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606, s. 603-608
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Tidskriftsartikel (refereegranskat)abstract
- Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.
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| 5. |
- Itoh, Yuzuru, et al.
(författare)
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Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules
- 2022
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Ingår i: eLIFE. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The mitoribosome regulates cellular energy production, and its dysfunction is associated with aging. Inhibition of the mitoribosome can be caused by off-target binding of antimicrobial drugs and was shown to be coupled with a bilateral decreased visual acuity. Previously, we reported mitochondria-specific protein aspects of the mitoribosome, and in this article we present a 2.4-Å resolution structure of the small subunit in a complex with the anti-tuberculosis drug streptomycin that reveals roles of non-protein components. We found iron–sulfur clusters that are coordinated by different mitoribosomal proteins, nicotinamide adenine dinucleotide (NAD) associated with rRNA insertion, and posttranslational modifications. This is the first evidence of inter-protein coordination of iron–sulfur, and the finding of iron–sulfur clusters and NAD as fundamental building blocks of the mitoribosome directly links to mitochondrial disease and aging. We also report details of streptomycin interactions, suggesting that the mitoribosome-bound streptomycin is likely to be in hydrated gem-diol form and can be subjected to other modifications by the cellular milieu. The presented approach of adding antibiotics to cultured cells can be used to define their native structures in a bound form under more physiological conditions, and since streptomycin is a widely used drug for treatment, the newly resolved features can serve as determinants for targeting.
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| 6. |
- Naschberger, Andreas, et al.
(författare)
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Algal photosystem I dimer and high-resolution model of PSI-plastocyanin complex
- 2022
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Ingår i: Nature Plants. - : Springer Science and Business Media LLC. - 2055-0278. ; 8:10, s. 1191-1201
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Tidskriftsartikel (refereegranskat)abstract
- Photosystem I (PSI) enables photo-electron transfer and regulates photosynthesis in the bioenergetic membranes of cyanobacteria and chloroplasts. Being a multi-subunit complex, its macromolecular organization affects the dynamics of photosynthetic membranes. Here we reveal a chloroplast PSI from the green alga Chlamydomonas reinhardtii that is organized as a homodimer, comprising 40 protein subunits with 118 transmembrane helices that provide scaffold for 568 pigments. Cryogenic electron microscopy identified that the absence of PsaH and Lhca2 gives rise to a head-to-head relative orientation of the PSI–light-harvesting complex I monomers in a way that is essentially different from the oligomer formation in cyanobacteria. The light-harvesting protein Lhca9 is the key element for mediating this dimerization. The interface between the monomers is lacking PsaH and thus partially overlaps with the surface area that would bind one of the light-harvesting complex II complexes in state transitions. We also define the most accurate available PSI–light-harvesting complex I model at 2.3 Å resolution, including a flexibly bound electron donor plastocyanin, and assign correct identities and orientations to all the pigments, as well as 621 water molecules that affect energy transfer pathways.
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| 7. |
- Singh, Vivek, et al.
(författare)
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Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In mammalian mitochondria, mRNAs are co-transcriptionally stabilized by the protein factor LRPPRC. Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-EM structure in complex with SLIRP, mRNA and the mitoribosome. The structure shows that LRPPRC associates with the mitoribosomal proteins mS39 and the N-terminus of mS31 through recognition of eight of the LRPPRC helical repeats. Together, the proteins form a corridor for hand-off the mRNA. The mRNA is directly bound to SLIRP, which also has a stabilizing function for LRPPRC. To delineate the effect of LRPPRC on individual mitochondrial transcripts, we used an RNAseq approach, metabolic labeling and mitoribosome profiling that showed a major influence onND1, ND2, ATP6, COX1, COX2,andCOX3mRNA translation efficiency. Taken together, our data suggest that LRPPRC-SLIRP does not preexist on the mitoribosome as its structural element but rather acts in recruitment of specific mRNAs to modulate their translation. Collectively, the data define LRPPRC-SLIRP as a regulator of the mitochondrial gene expression system.
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| 8. |
- Tobiasson, Victor, 1994-
(författare)
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On the Origin and Evolution of the Mitochondrial Ribosome
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ribosome is among the most ancient, intricate and well studied macromolecular complexes in biology. Predating the earliest divergence of life, its core molecular structure has remained mostly unchanged for more than three billion years. In stark contrast to its monolithic ancestor, the mitochondrial ribosome represents one of the most architecturally diverse protein complexes investigated. This work is an attempt at reconciling these two paradigms. In this thesis I first briefly cover the evolutionary history of the mitochondrial ribosome: from its ancient origins, through the process of Eukaryogenesis and the development of mitochondria, to its current state. Following this I present a comprehensive and integrated comparative analysis of the current mitoribosomal structures. Using these structural observations as a starting point I then summarise the current knowledge regarding the evolutionary trends of mitochondrial ribosomes. Finally I review and discuss potential genetic mechanisms and evolutionary pressures which could have produced such a vibrant diversity of structures. Together with this analysis I present monosome structures from the ciliate Tetrahymena thermophila and chlorophycean Polytomella magna together with an assembly intermediate of the large subunit from Trypanosoma brucei. Together, I hope to demonstrate the impact of the unique mitochondrial environment on the evolution of the mitochondrial ribosome.
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| 9. |
- Tobiasson, Victor, et al.
(författare)
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Structure of a mitochondrial ribosome with fragmented rRNA in complex with membrane-targeting elements
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitoribosomes of green algae display a great structural divergence from their tracheophyte relatives, with fragmentation of both rRNA and proteins as a defining feature. Here, we report a 2.9 angstrom resolution structure of the mitoribosome from the alga Polytomella magna harbouring a reduced rRNA split into 13 fragments. We found that the rRNA contains a non-canonical reduced form of the 5S, as well as a permutation of the LSU domain I. The mt-5S rRNA is stabilised by mL40 that is also found in mitoribosomes lacking the 5S, which suggests an evolutionary pathway. Through comparison to other ribosomes with fragmented rRNAs, we observe that the pattern is shared across large evolutionary distances, and between cellular compartments, indicating an evolutionary convergence and supporting the concept of a primordial fragmented ribosome. On the protein level, eleven peripherally associated HEAT-repeat proteins are involved in the binding of 3' rRNA termini, and the structure features a prominent pseudo-trimer of one of them (mL116). Finally, in the exit tunnel, mL128 constricts the tunnel width of the vestibular area, and mL105, a homolog of a membrane targeting component mediates contacts with an inner membrane bound insertase. Together, the structural analysis provides insight into the evolution of the ribosomal machinery in mitochondria.
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