Computed structures of core eukaryotic protein complexes

Science, Год журнала: 2021, Номер 374(6573)

Опубликована: Ноя. 11, 2021

Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there likely not yet identified. We take advantage advances proteome-wide amino acid coevolution analysis deep-learning–based structure modeling to systematically identify build accurate models core within

Язык: Английский

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A comprehensive review of m6A/m6Am RNA methyltransferase structures

Nucleic Acids Research, Год журнала: 2021, Номер 49(13), С. 7239 - 7255

Опубликована: Апрель 26, 2021

Abstract Gene expression is regulated at many levels including co- or post-transcriptionally, where chemical modifications are added to RNA on riboses and bases. Expression control via has been termed ‘epitranscriptomics’ keep with the related ‘epigenomics’ for DNA modification. One such modification N6-methylation found adenosine (m6A) 2′-O-methyladenosine (m6Am) in most types of RNA. The can affect fold, stability, degradation cellular interaction(s) modified RNA, implicating it processes as splicing, translation, export decay. multiple roles played by this explains why m6A misregulation connected human cancers. m6A/m6Am writer enzymes methyltransferases (MTases). Structures available functionally characterized MTases from (m6A mRNA, snRNA, rRNA m6Am mRNA MTases), zebrafish (m6Am MTase) bacteria MTase). For each these MTases, we describe their overall domain organization, active site architecture substrate binding. We identify areas that remain be investigated, propose yet unexplored routes structural characterization MTase:substrate complexes, highlight common elements should described future MTase structures.

Язык: Английский

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Origin and Evolution of the Ribosome

Cold Spring Harbor Perspectives in Biology, Год журнала: 2010, Номер 2(9), С. a003483 - a003483

Опубликована: Июнь 9, 2010

The modern ribosome was largely formed at the time of last common ancestor, LUCA. Hence its earliest origins likely lie in RNA world. Central to development were RNAs that spawned tRNAs and a symmetrical region deep within large ribosomal RNA, (rRNA), where peptidyl transferase reaction occurs. To understand pre-LUCA developments, it is argued events are coupled especially useful if one can infer order which they occurred. Using such timing events, relative age various proteins individual regions rRNA inferred. An examination properties ribosomes strongly suggests initial peptides made by primitive enriched for l-amino acids, but did not completely exclude d-amino acids. This has implications nature first ribosomes. From perspective origins, immediate question regarding coding when arise rather than how assignments evolve. very dynamic with moving out mRNA ribosome. These movements may have become possible as result addition template hold tRNAs. That would subsequently mRNA, thereby allowing evolution code making an genome useful. Finally, highly speculative timeline major history presented future directions discussed.

Язык: Английский

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ArtiaX: An electron tomography toolbox for the interactive handling of sub‐tomograms in UCSF ChimeraX

Protein Science, Год журнала: 2022, Номер 31(12)

Опубликована: Окт. 17, 2022

Abstract Cryo‐electron tomography analysis involves the selection of macromolecular complexes to be used for subsequent sub‐tomogram averaging and structure determination. Here, we describe a plugin developed UCSF ChimeraX that allows display, selection, editing particles within tomograms. Positions orientations selected can manually set, modified inspected in real time, both on screen virtual reality, exported various file formats. The parallel visualization stored several meta data lists, context any three‐dimensional image opened with ChimeraX. are rendered user‐defined colors or using colormaps, such individual classes groups particles, cross‐correlation coefficients, other types information highlighted user. implemented functions fast, reliable, intuitive, exploring broad range features They allow fluent human–machine interaction, which enables an effective understanding processing pipeline, even non‐specialist users.

Язык: Английский

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Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 13(3), С. 916 - 941

Опубликована: Окт. 27, 2022

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets diagnostic biomarkers. However, efficient delivery RNA to targeted location precise detection markers remains challenging. Recently, more attention has been paid applying nucleic acid nanoassemblies diagnosing treating. Due flexibility deformability acids, could be fabricated with different shapes structures. With hybridization, nanoassemblies, including DNA nanostructures, can applied enhance therapeutics diagnosis. This review briefly introduces construction properties their applications for therapy diagnosis makes further prospects development.

Язык: Английский

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Structural conservation of antibiotic interaction with ribosomes

Nature Structural & Molecular Biology, Год журнала: 2023, Номер 30(9), С. 1380 - 1392

Опубликована: Авг. 7, 2023

The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete. Here we present cryo-electron-microscopy structures 17 distinct compounds from six different antibiotic classes bound to the bacterial at resolutions ranging 1.6 2.2 Å. improved resolution enables precise description antibiotic-ribosome interactions, encompassing solvent networks that mediate multiple additional interactions between drugs and their target. Our results reveal high structural conservation in binding mode antibiotics with same scaffold, including ordered water molecules. Water molecules visualized within sites preordered, become presence drug physically displaced on binding. Insight into RNA-ligand will facilitate development new antimicrobial agents, as well other RNA-targeting therapies.

Язык: Английский

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The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Фев. 25, 2023

Abstract Our understanding of protein synthesis has been conceptualised around the structure and function bacterial ribosome. This complex macromolecular machine is target important antimicrobial drugs, an integral line defence against infectious diseases. Here, we describe how open access to cryo-electron microscopy facilities combined with bespoke user support enabled structural determination translating ribosome from Escherichia coli at 1.55 Å resolution. The obtained structures allow for direct rRNA sequence identify polymorphism sites in E. strain used this study enable interpretation ribosomal active peripheral unprecedented includes scarcely populated chimeric hybrid states engaged several tRNA translocation steps resolved ~2 current map not only improves our but also allows more precise structure-based drug design antibiotics tackle rising resistance.

Язык: Английский

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The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA

Nature Structural & Molecular Biology, Год журнала: 2024, Номер 31(8), С. 1251 - 1264

Опубликована: Июнь 6, 2024

Язык: Английский

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Metals in Motion: Understanding Labile Metal Pools in Bacteria

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

Metal ions are essential for all life. In microbial cells, potassium (K+) is the most abundant cation and plays a key role in maintaining osmotic balance. Magnesium (Mg2+) dominant divalent required nucleic acid structure as an enzyme cofactor. Microbes typically require transition metals manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), although precise set of metal needed to sustain life variable. Intracellular pools can be conceptualized chemically complex mixture rapidly exchanging (labile) ions, complemented by those reservoirs that exchange slowly relative cell metabolism (sequestered). Labile buffered transient interactions with anionic metabolites macromolecules, ribosome playing major role. Sequestered include many metalloproteins, cofactors, storage depots, some redeployed upon depletion. Here, I review size, composition, dynamics intracellular highlight gaps understanding.

Язык: Английский

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Translational Control by Ribosome Pausing in Bacteria: How a Non-uniform Pace of Translation Affects Protein Production and Folding

Frontiers in Microbiology, Год журнала: 2021, Номер 11

Опубликована: Янв. 11, 2021

Protein homeostasis of bacterial cells is maintained by coordinated processes protein production, folding, and degradation. Translational efficiency a given mRNA depends on how often the ribosomes initiate synthesis new polypeptide quickly they read coding sequence to produce full-length protein. The pace along not uniform: periods rapid are separated pauses. Here, we summarize recent evidence ribosome pausing affects translational folding. We discuss factors that slow down translation elongation affect quality newly synthesized Ribosome emerges as important factor contributing regulatory programs ensure proteome integrate cellular environmental cues into circuits cell.

Язык: Английский

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