scholarly journals Nuclear magnetic resonance studies of ribonucleic acids

2003 ◽  
Vol 17 (2-3) ◽  
pp. 537-547 ◽  
Author(s):  
Oliver Ohlenschläger ◽  
Jens Wöhnert ◽  
Ramadurai Ramachandran ◽  
Christian Sich ◽  
Matthias Görlach
Keyword(s):  
Information Transfer ◽  
Residual Dipolar Couplings ◽  
Protein Complexes ◽  
Pulse Sequences ◽  
Biological Information ◽  
Base Pairs ◽  
Stable Isotope Labelling ◽  
Ribonucleic Acids ◽  
Hydrogen Bonding Pattern ◽  
Essential Components

Ribonucleic acids (RNA) and RNA−protein complexes are essential components of biological information transfer, catalytic processes and are associated with regulatory functions. This broad range of biological functions is paralleled at the conformational level by a large number of non-canonical structural elements or sequences with non-standard backbone conformations, e.g., loops, bulges, pseudo-knots and complex tertiary folds. NMR spectroscopy has evolved to a powerful tool for the determination of ribonucleic acid structures of up to 20 kDa. Uniform or selective stable isotope labelling aids in solving assignment problems arising from the inherently limited chemical shift dispersion and overlap of resonances for larger nucleotide sequences. Recent developments of multi-dimensional heteronuclear NMR pulse sequences allow e.g., to directly observe the hydrogen bonding pattern of canonical Watson−Crick base pairs as well as of unusual types of base pairs, thereby opening up a fast access to secondary structure screening of RNA. Detailed conformational descriptions are obtained using conventional NOE andJcoupling-derived data, nowadays supplemented by information from residual dipolar couplings. The latter method also provides a new means for the probing of dynamical features of ribonucleic acids.

scholarly journals Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

2018 ◽  
Vol 475 (3) ◽  
pp. 587-620 ◽  
Author(s):  
Anthony Hayes ◽  
Kazuyuki Sugahara ◽  
Brooke Farrugia ◽  
John M. Whitelock ◽  
Bruce Caterson ◽  
...  
Keyword(s):  
Information Transfer ◽  
Enzyme Inhibitors ◽  
Chondroitin Sulphate ◽  
Chain Structure ◽  
Bioactive Molecules ◽  
Biological Information ◽  
Extracellular Milieu ◽  
Overwhelming Evidence ◽  
Chemical Messenger ◽  
Cellular Behaviour

Chondroitin sulphate (CS) glycosaminoglycan chains on cell and extracellular matrix proteoglycans (PGs) can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the CS chain structure are a source of significant biological information to cells and their surrounding environment. CS sulphation motifs have been shown to interact with a wide variety of bioactive molecules, e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways, thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, CS PGs play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here, we review (i) the biodiversity of CS PGs and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repair.

scholarly journals DRP1 regulates endoplasmic reticulum sheets to control mitochondrial DNA replication and segregation

2021 ◽  
Author(s):  
Hema Saranya Ilamathi ◽  
Sara Benhammouda ◽  
Justine Desrochers-Goyette ◽  
Matthew A Lines ◽  
Marc Germain
Keyword(s):  
Endoplasmic Reticulum ◽  
Mitochondrial Dna ◽  
Protein Complexes ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Diseases ◽  
Contact Sites ◽  
Transport Chain ◽  
Essential Components ◽  
Mtdna Replication

Mitochondria are multi-faceted organelles crucial for cellular homeostasis that contain their own genome. Mitochondrial DNA (mtDNA) codes for several essential components of the electron transport chain, and mtDNA maintenance defects lead to mitochondrial diseases. mtDNA replication occurs at endoplasmic reticulum (ER)-mitochondria contact sites and is regulated by mitochondrial dynamics. Specifically, mitochondrial fusion is essential for mtDNA maintenance. In contrast, while loss of mitochondrial fission causes the aggregation of nucleoids (mtDNA-protein complexes), its role in nucleoid distribution remains unclear. Here, we show that the mitochondrial fission protein DRP1 regulates nucleoid segregation by altering ER sheets, the ER structure associated with protein synthesis. Specifically, DRP1 loss or mutation leads to altered ER sheets that physically interact with mitobulbs, mitochondrial structures containing aggregated nucleoids. Importantly, nucleoid distribution and mtDNA replication were rescued by expressing the ER sheet protein CLIMP63. Thus, our work identifies a novel mechanism by which DRP1 regulates mtDNA replication and distribution.

scholarly journals Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5078 ◽  
Author(s):  
Walter J. Lukiw ◽  
Aileen I. Pogue
Keyword(s):  
Information Transfer ◽  
Biological Information ◽  
Messenger Rnas ◽  
Innate Immune Signaling ◽  
Cells Of Origin ◽  
Metabolic Products ◽  
Inflammatory Phenotype ◽  
The Central Nervous System ◽  
Neuro Inflammation ◽  
End Stage

Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30–1000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (Aβ) peptides. Brain microglia, for example, respond to both acute CNS injuries and degenerative diseases with complex reactions via the induction of a pro-inflammatory phenotype, and secrete EXs and EMVs enriched in selective pathogenic microRNAs (miRNAs) such as miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155, and others that are known to promote neuro-inflammation, induce complement activation, disrupt innate–immune signaling and deregulate the expression of neuron-specific phosphoproteins involved in neurotropism and synaptic signaling. This communication will review our current understanding of the trafficking of miRNA-containing EXs and EMVs from astrocytes and “activated pro-inflammatory” microglia to target neurons in neurodegenerative diseases with an emphasis on Alzheimer’s disease wherever possible.

scholarly journals Real-time imaging of DNA loop extrusion by condensin

Science ◽  
2018 ◽  
Vol 360 (6384) ◽  
pp. 102-105 ◽  
Author(s):  
Mahipal Ganji ◽  
Indra A. Shaltiel ◽  
Shveta Bisht ◽  
Eugene Kim ◽  
Ana Kalichava ◽  
...  
Keyword(s):  
Real Time ◽  
Adenosine Triphosphate ◽  
Genome Organization ◽  
Protein Complexes ◽  
Dna Loops ◽  
Base Pairs ◽  
Real Time Imaging ◽  
Condensin Complex ◽  
Dna Loop

It has been hypothesized that SMC protein complexes such as condensin and cohesin spatially organize chromosomes by extruding DNA into large loops. We directly visualized the formation and processive extension of DNA loops by yeast condensin in real time. Our findings constitute unambiguous evidence for loop extrusion. We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis. Condensin-induced loop extrusion was strictly asymmetric, which demonstrates that condensin anchors onto DNA and reels it in from only one side. Active DNA loop extrusion by SMC complexes may provide the universal unifying principle for genome organization.

scholarly journals Conserved Central Intraviral Protein Interactome of the Herpesviridae Family

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Anna Hernández Durán ◽  
Kay Grünewald ◽  
Maya Topf
Keyword(s):  
Protein Interactions ◽  
Computational Models ◽  
Functional Organization ◽  
Driving Forces ◽  
Protein Complexes ◽  
Structural Features ◽  
System Level ◽  
Protein Protein Interactions ◽  
Protein Interactome ◽  
Essential Components

ABSTRACT Protein interactions are major driving forces behind the functional phenotypes of biological processes. As such, evolutionary footprints are reflected in system-level collections of protein-protein interactions (PPIs), i.e., protein interactomes. We conducted a comparative analysis of intraviral protein interactomes for representative species of each of the three subfamilies of herpesviruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus), which are highly prevalent etiologic agents of important human diseases. The intraviral interactomes were reconstructed by combining experimentally supported and computationally predicted protein-protein interactions. Using cross-species network comparison, we then identified family-wise conserved interactions and protein complexes, which we defined as a herpesviral “central” intraviral protein interactome. A large number of widely accepted conserved herpesviral protein complexes are present in this central intraviral interactome, encouragingly supporting the biological coherence of our results. Importantly, these protein complexes represent most, if not all, of the essential steps required during a productive life cycle. Hence the central intraviral protein interactome could plausibly represent a minimal infectious interactome of the herpesvirus family across a variety of hosts. Our data, which have been integrated into our herpesvirus interactomics database, HVint2.0, could assist in creating comprehensive system-level computational models of this viral lineage. IMPORTANCE Herpesviruses are an important socioeconomic burden for both humans and livestock. Throughout their long evolutionary history, individual herpesvirus species have developed remarkable host specificity, while collectively the Herpesviridae family has evolved to infect a large variety of eukaryotic hosts. The development of approaches to fight herpesvirus infections has been hampered by the complexity of herpesviruses’ genomes, proteomes, and structural features. The data and insights generated by our study add to the understanding of the functional organization of herpesvirus-encoded proteins, specifically of family-wise conserved features defining essential components required for a productive infectious cycle across different hosts, which can contribute toward the conceptualization of antiherpetic infection strategies with an effect on a broader range of target species. All of the generated data have been made freely available through our HVint2.0 database, a dedicated resource of curated herpesvirus interactomics purposely created to promote and assist future studies in the field.

scholarly journals Functional geometry of protein interactomes

2019 ◽  
Vol 35 (19) ◽  
pp. 3727-3734 ◽  
Author(s):  
Noël Malod-Dognin ◽  
Nataša Pržulj
Keyword(s):  
Functional Organization ◽  
Protein Complexes ◽  
Simplicial Complexes ◽  
Higher Order ◽  
Biological Information ◽  
Supplementary Information ◽  
Data Types ◽  
Ppi Networks ◽  
Functional Geometry ◽  
Better Than

Abstract Motivation Protein–protein interactions (PPIs) are usually modeled as networks. These networks have extensively been studied using graphlets, small induced subgraphs capturing the local wiring patterns around nodes in networks. They revealed that proteins involved in similar functions tend to be similarly wired. However, such simple models can only represent pairwise relationships and cannot fully capture the higher-order organization of protein interactomes, including protein complexes. Results To model the multi-scale organization of these complex biological systems, we utilize simplicial complexes from computational geometry. The question is how to mine these new representations of protein interactomes to reveal additional biological information. To address this, we define simplets, a generalization of graphlets to simplicial complexes. By using simplets, we define a sensitive measure of similarity between simplicial complex representations that allows for clustering them according to their data types better than clustering them by using other state-of-the-art measures, e.g. spectral distance, or facet distribution distance. We model human and baker’s yeast protein interactomes as simplicial complexes that capture PPIs and protein complexes as simplices. On these models, we show that our newly introduced simplet-based methods cluster proteins by function better than the clustering methods that use the standard PPI networks, uncovering the new underlying functional organization of the cell. We demonstrate the existence of the functional geometry in the protein interactome data and the superiority of our simplet-based methods to effectively mine for new biological information hidden in the complexity of the higher-order organization of protein interactomes. Availability and implementation Codes and datasets are freely available at http://www0.cs.ucl.ac.uk/staff/natasa/Simplets/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Clustering based on multiple biological information: approach for predicting protein complexes

2013 ◽  
Vol 7 (5) ◽  
pp. 223-230 ◽  
Author(s):  
Xiwei Tang ◽  
Qilong Feng ◽  
Jianxin Wang ◽  
Yiming He ◽  
Yi Pan
Keyword(s):  
Protein Complexes ◽  
Biological Information ◽  
Information Approach

Oligomeric assembly and interactions within the human RuvB-like RuvBL1 and RuvBL2 complexes

2010 ◽  
Vol 429 (1) ◽  
pp. 113-125 ◽  
Author(s):  
Andrew Niewiarowski ◽  
Alison S. Bradley ◽  
Jayesh Gor ◽  
Adam R. McKay ◽  
Stephen J. Perkins ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Structural Model ◽  
Analytical Ultracentrifugation ◽  
Protein Complexes ◽  
Adenine Nucleotides ◽  
Size Exclusion ◽  
Molecular Architecture ◽  
Essential Components ◽  
Exclusion Chromatography

The two closely related eukaryotic AAA+ proteins (ATPases associated with various cellular activities), RuvBL1 (RuvB-like 1) and RuvBL2, are essential components of large multi-protein complexes involved in diverse cellular processes. Although the molecular mechanisms of RuvBL1 and RuvBL2 function remain unknown, oligomerization is likely to be important for their function together or individually, and different oligomeric forms might underpin different functions. Several experimental approaches were used to investigate the molecular architecture of the RuvBL1–RuvBL2 complex and the role of the ATPase-insert domain (domain II) for its assembly and stability. Analytical ultracentrifugation showed that RuvBL1 and RuvBL2 were mainly monomeric and each monomer co-existed with small proportions of dimers, trimers and hexamers. Adenine nucleotides induced hexamerization of RuvBL2, but not RuvBL1. In contrast, the RuvBL1–RuvBL2 complexes contained single- and double-hexamers together with smaller forms. The role of domain II in complex assembly was examined by size-exclusion chromatography using deletion mutants of RuvBL1 and RuvBL2. Significantly, catalytically competent dodecameric RuvBL1–RuvBL2, complexes lacking domain II in one or both proteins could be assembled but the loss of domain II in RuvBL1 destabilized the dodecamer. The composition of the RuvBL1–RuvBL2 complex was analysed by MS. Several species of mixed RuvBL1/2 hexamers with different stoichiometries were seen in the spectra of the RuvBL1–RuvBL2 complex. A number of our results indicate that the architecture of the human RuvBL1–RuvBL2 complex does not fit the recent structural model of the yeast Rvb1–Rvb2 complex.

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