CircRNP complexes: from nature to design.
Ontology highlight
ABSTRACT:
SUBMITTER: Nuthalapati SS
PROVIDER: S-EPMC10234438 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
Publications
CircRNP complexes: from nature to design.
Nuthalapati Stephen Sukumar SS Ulshöfer Corinna Jessica CJ Bindereif Albrecht A
Journal of molecular cell biology 20230601 1
Similar Datasets
Project description: Not available
| S-EPMC4888937 | biostudies-literature
Project description:Protein conformational switches alter their shape upon receiving an input signal, such as ligand binding, chemical modification, or change in environment. The apparent simplicity of this transformation--which can be carried out by a molecule as small as a thousand atoms or so--belies its critical importance to the life of the cell as well as its capacity for engineering by humans. In the realm of molecular switches, proteins are unique because they are capable of performing a variety of biological functions. Switchable proteins are therefore of high interest to the fields of biology, biotechnology, and medicine. These molecules are beginning to be exploited as the core machinery behind a new generation of biosensors, functionally regulated enzymes, and "smart" biomaterials that react to their surroundings. As inspirations for these designs, researchers continue to analyze existing examples of allosteric proteins. Recent years have also witnessed the development of new methodologies for introducing conformational change into proteins that previously had none. Herein we review examples of both natural and engineered protein switches in the context of four basic modes of conformational change: rigid-body domain movement, limited structural rearrangement, global fold switching, and folding-unfolding. Our purpose is to highlight examples that can potentially serve as platforms for the design of custom switches. Accordingly, we focus on inducible conformational changes that are substantial enough to produce a functional response (e.g., in a second protein to which it is fused), yet are relatively simple, structurally well-characterized, and amenable to protein engineering efforts.
| S-EPMC3404493 | biostudies-literature
Project description:Aberrant changes in post-translational modifications (PTMs) such as phosphate groups underlie a majority of human diseases. However, detection and quantification of PTMs for diagnostic or biomarker applications often require PTM-specific monoclonal antibodies (mAbs), which are challenging to generate using traditional antibody-selection methods. Here we outline a general strategy for producing synthetic, PTM-specific mAbs by engineering a motif-specific 'hot spot' into an antibody scaffold. Inspired by a natural phosphate-binding motif, we designed and selected mAb scaffolds with hot spots specific for phosphoserine, phosphothreonine or phosphotyrosine. Crystal structures of the phospho-specific mAbs revealed two distinct modes of phosphoresidue recognition. Our data suggest that each hot spot functions independently of the surrounding scaffold, as phage display antibody libraries using these scaffolds yielded >50 phospho- and target-specific mAbs against 70% of target peptides. Our motif-specific scaffold strategy may provide a general solution for rapid, robust development of anti-PTM mAbs for signaling, diagnostic and therapeutic applications.
| S-EPMC3795957 | biostudies-literature
Project description:Homogeneous catalysis by gold involves organogold complexes as precatalysts and reaction intermediates. Fundamental knowledge of the gold-carbon bonding is critical to understanding the catalytic mechanisms. However, limited spectroscopic information is available about organogolds that are relevant to gold catalysts. Here we report an investigation of the gold-carbon bonding in gold(I)-alkynyl complexes using photoelectron spectroscopy and theoretical calculations. We find that the gold-carbon bond in the ClAu-CCH(-) complex represents one of the strongest gold-ligand bonds-even stronger than the known gold-carbon multiple bonds, revealing an inverse correlation between bond strength and bond order. The gold-carbon bond in LAuCCH(-) is found to depend on the ancillary ligands and becomes stronger for more electronegative ligands. The strong gold-carbon bond underlies the catalytic aptness of gold complexes for the facile formation of terminal alkynyl-gold intermediates and activation of the carbon-carbon triple bond.
| S-EPMC5882230 | biostudies-literature
Project description:Benchmark quality geometries and interaction energies for the prereactive halogen-bonded complexes of dihalogens and ammonia, including hypothetical astatine containing dihalogens, have been produced via explicitly correlated coupled cluster methods. The application of local electron correlation partitioning reveals dispersion, electrostatics and ionic substitutions all contribute significantly to the interaction energy, with a linear relationship between the ionic substitutions and the degree of charge transfer. Potential energy curves for H3 N⋅⋅⋅ClF show that as the relative orientations of the two subunits are manipulated appreciable interactions can be found at considerably angular displaced geometries, signifying lower directionality in halogen bonding than previously supposed.
| S-EPMC3790957 | biostudies-literature
Project description:Increasingly prevalent extreme weather events have caused resilience to become an essential sustainable development component for resource and infrastructure networks. Existing resilience metrics require detailed knowledge of the system and potential disruptions, which is not available in the early design stage. The lack of quantitative tools to guide the early stages of design for resilience, forces engineers to rely on heuristics (use physical redundancy, localized capacity, etc.). This research asserts that the required quantitative guidelines can be developed using the architecting principles of biological ecosystems, which maintain a unique balance between pathway redundancy and efficiency, enabling them to be both productive under normal circumstances and survive disruptions. Ecologists quantify this network characteristic using the ecological fitness function. This paper presents the required reformulation required to enable the use of this metric in the design and analysis of resource and infrastructure networks with multiple distinct, but interdependent, interactions. The proposed framework is validated by comparing the resilience characteristics of two notional supply chain designs: one designed for minimum shipping cost and the other designed using the proposed bio-inspired framework. The results support using the proposed bio-inspired framework to guide designers in creating resilient and sustainable resource and infrastructure networks.
| S-EPMC7385727 | biostudies-literature
Project description:The inhibition of cysteine biosynthesis in prokaryotes and protozoa has been proposed to be relevant for the development of antibiotics. Haemophilus influenzae O-acetylserine sulfhydrylase (OASS), catalyzing l-cysteine formation, is inhibited by the insertion of the C-terminal pentapeptide (MNLNI) of serine acetyltransferase into the active site. Four-hundred MNXXI pentapeptides were generated in silico, docked into OASS active site using GOLD, and scored with HINT. The terminal P5 Ile accounts for about 50% of the binding energy. Glu or Asp at position P4 and, to a lesser extent, at position P3 also significantly contribute to the binding interaction. The predicted affinity of 14 selected pentapeptides correlated well with the experimentally determined dissociation constants. The X-ray structure of three high affinity pentapeptide-OASS complexes were compared with the docked poses. These results, combined with a GRID analysis of the active site, allowed us to define a pharmacophoric scaffold for the design of peptidomimetic inhibitors.
| S-EPMC2804909 | biostudies-literature
Project description:In plants, sinapate esters offer crucial protection from the deleterious effects of ultraviolet radiation exposure. These esters are a promising foundation for designing UV filters, particularly for the UVA region (400 - 315 nm), where adequate photoprotection is currently lacking. Whilst sinapate esters are highly photostable due to a cis-trans (and vice versa) photoisomerization, the cis-isomer can display increased genotoxicity; an alarming concern for current cinnamate ester-based human sunscreens. To eliminate this potentiality, here we synthesize a sinapate ester with equivalent cis- and trans-isomers. We investigate its photostability through innovative ultrafast spectroscopy on a skin mimic, thus modelling the as close to true environment of sunscreen formulas. These studies are complemented by assessing endocrine disruption activity and antioxidant potential. We contest, from our results, that symmetrically functionalized sinapate esters may show exceptional promise as nature-inspired UV filters in next generation sunscreen formulations.
| S-EPMC6802189 | biostudies-literature
Project description:Antibodies that recognize amyloidogenic aggregates with high conformational and sequence specificity are important for detecting and potentially treating a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. However, these types of antibodies are challenging to generate because of the large size, hydrophobicity, and heterogeneity of protein aggregates. To address this challenge, we developed a method for generating antibodies specific for amyloid aggregates. First, we grafted amyloidogenic peptide segments from the target polypeptide [Alzheimer's amyloid-β (Aβ) peptide] into the complementarity-determining regions (CDRs) of a stable antibody scaffold. Next, we diversified the grafted and neighboring CDR sites using focused mutagenesis to sample each WT or grafted residue, as well as one to five of the most commonly occurring amino acids at each site in human antibodies. Finally, we displayed these antibody libraries on the surface of yeast cells and selected antibodies that strongly recognize Aβ-amyloid fibrils and only weakly recognize soluble Aβ. We found that this approach enables the generation of monovalent and bivalent antibodies with nanomolar affinity for Aβ fibrils. These antibodies display high conformational and sequence specificity as well as low levels of nonspecific binding and recognize a conformational epitope at the extreme N terminus of human Aβ. We expect that this systematic approach will be useful for generating antibodies with conformational and sequence specificity against a wide range of peptide and protein aggregates associated with neurodegenerative disorders.
| S-EPMC6544860 | biostudies-literature
Project description:Bio-inorganic complexes inspired by hydrogenase enzymes are designed to catalyze the hydrogen evolution reaction (HER). A series of new diiron hydrogenase mimic complexes with one or two terminal tris(4-methoxyphenyl)phosphine and different μ-bridging dithiolate ligands and show catalytic activity towards electrochemical proton reduction in the presence of weak and strong acids. A series of propane- and benzene-dithiolato-bridged complexes was synthesized, crystallized, and characterized by various spectroscopic techniques and quantum chemical calculations. Their electrochemical properties as well as the detailed reaction mechanisms of the HER are elucidated by density functional theory (DFT) methods. The nature of the μ-bridging dithiolate is critically controlling the reaction and performance of the HER of the complexes. In contrast, terminal phosphine ligands have no significant effects on redox activities and mechanism. Mono- or di-substituted propane-dithiolate complexes afford a sequential reduction (electrochemical; E) and protonation (chemical; C) mechanism (ECEC), while the μ-benzene dithiolate complexes follow a different reaction mechanism and are more efficient HER catalysts.
| S-EPMC8734113 | biostudies-literature