Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.08.22.504886

RiboXYZ: A comprehensive database for visualizing and analyzing ribosomestructures

Abstract

Recent advances in Cryo-EM led to a surge of ribosome structures deposited over the past years, including structures from different species, conformational states, or bound with different ligands. Yet, multiple conflicts of nomenclature make the identification and comparison of structures and ortholog components challenging. We present RiboXYZ (available at https://ribosome.xyz), a database that provides organized access to ribosome structures, with several tools for visualisation and study. The database is up-to-date with the Protein Data Bank (PDB) but provides a standardized nomenclature that allows for searching and comparing ribosomal components (proteins, RNA, ligands) across all the available structures. In addition to structured and simplified access to the data, the application has several specialized visualization tools, including the identification and prediction of ligand binding sites, and 3D superimposition of ribosomal components. Overall, RiboXYZ provides a useful toolkit that complements the PDB database, by implementing the current conventions and providing a set of auxiliary tools that have been developed explicitly for analyzing ribosome structures. This toolkit can be easily accessible by both experts and non-experts in structural biology so that they can search, visualize and compare structures, with various potential applications in molecular biology, evolution, and biochemistry.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kushner, A., Petrov, A. S., Dao Duc, K.. 2022-08-23. RiboXYZ: A comprehensive database for visualizing and analyzing ribosomestructures. https://doi.org/10.1101/2022.08.22.504886

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A G-Quadruplex Containing First Intron Harbors a Functional Polyadenylation Signal in TP53

First introns of mammalian genes are often longer than other introns and may contain regulatory elements, suggesting that they may have roles in gene regulation. We detected a previously unannotated, low abundance intronic transcript, TP53-INT1, using long-read direct RNA sequencing data. TP53-INT1 has low coding potential and terminates within the first and longest intron of TP53. The transcript structure and 3'-end were validated by independent experimental and in silico evidence. We identified a canonical polyadenylation signal upstream of the transcript termination site and demonstrated its functionality using reporter assays. Furthermore, a potential G-quadruplex (G4)-forming sequence was identified upstream of this polyadenylation signal. The G4-forming potential was confirmed using spectroscopic and thermal stability analyses. Complementing the in vitro characterizations, treatment with Pyridostatin, a G4-stabilizing drug, was associated with decreased TP53 expression. Together, these findings characterize a previously unannotated TP53 intronic transcript and reveal a local genomic context combining accessible chromatin, a functional polyadenylation signal, and a potential G4-forming sequence that may influence full-length transcription.

molecular biology↗

An architectural RNA builds a reaction crucible through molecular concentration and activated enzyme selection

Architectural RNAs (arcRNAs) scaffold membraneless organelles (MLOs), yet how they organize functional proteins remains unclear. Nuclear stress bodies (nSBs), MLOs scaffolded by HSATIII arcRNAs, incorporate SRSFs during stress. During stress recovery, nSBs function as reaction crucibles that recruit the kinase CLK1 to accelerate SRSF rephosphorylation and normalize stress-induced splicing. Here, we identify the ASAP complex as a recruitment factor that recognizes Ser341-phosphorylated, catalytically activated CLK1. HSATIII-bound SRSFs recruit ASAP, assembling a platform for CLK1 recruitment. Biochemical reconstitution reveals that this platform enhances SRSF phosphorylation by concentrating SRSFs and CLK1 while selectively recruiting activated CLK1, establishing nSB reaction crucibles as molecular concentrators and selectors. The SRSF-ASAP-CLK1 interaction network is conserved between humans and mice, suggesting that primate-specific HSATIII arcRNAs co-opted this pre-existing network to establish reaction-crucible function in nSBs. Our findings reveal how arcRNAs organize functional proteins through quantitative enrichment and qualitative selection to build biochemically active MLOs.

molecular biology↗

Adult-like thick-filament protein stoichiometry in immature human iPSC-derived cardiomyocytes

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) retain immature sarcomeric isoforms, raising questions about their ability to recapitulate the protein stoichiometry of adult human myocardium. We integrated two independent quantitative proteomic datasets of iPSC-CMs with published fetal and region-resolved adult human heart proteomes to compare sarcomeric protein abundance. Although iPSC-CMs clustered with fetal heart based on their global shared proteome and retained fetal troponin I expression, key thick-filament protein ratios closely matched those of adult myocardium. Myosin heavy-to-light chain ratios approached the expected 2:4 stoichiometry, while myosin-binding protein abundance relative to myosin heavy chains was comparable across iPSC-CMs and adult cardiac regions. These findings reveal that developmental immaturity in sarcomeric isoform expression does not entail altered thick-filament protein proportions. Preservation of adult-like myosin-binding protein stoichiometry supports the use of iPSC-CMs to investigate sarcomeric diseases associated with altered protein dosage, particularly MYBPC3-associated hypertrophic cardiomyopathy.

molecular biology↗