Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Allosterism and signal transfer in DNA.

ABSTRACT: We analysed the basic mechanisms of signal transmission in DNA and the origins of the allostery exhibited by systems such as the ternary complex BAMHI-DNA-GRDBD. We found that perturbation information generated by a primary protein binding event travels as a wave to distant regions of DNA following a hopping mechanism. However, such a structural perturbation is transient and does not lead to permanent changes in the DNA geometry and interaction properties at the secondary binding site. The BAMHI-DNA-GRDBD allosteric mechanism does not occur through any traditional models: direct (protein-protein), indirect (reorganization of the secondary site) readout or solvent-release. On the contrary, it is generated by a subtle and less common entropy-mediated mechanism, which might have an important role to explain other DNA-mediated cooperative effects.

SUBMITTER: Balaceanu A

PROVIDER: S-EPMC6125689 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Allosterism and signal transfer in DNA.

Balaceanu Alexandra A Pérez Alberto A Dans Pablo D PD Orozco Modesto M

Nucleic acids research 20180901 15

We analysed the basic mechanisms of signal transmission in DNA and the origins of the allostery exhibited by systems such as the ternary complex BAMHI-DNA-GRDBD. We found that perturbation information generated by a primary protein binding event travels as a wave to distant regions of DNA following a hopping mechanism. However, such a structural perturbation is transient and does not lead to permanent changes in the DNA geometry and interaction properties at the secondary binding site. The BAMHI ...[more]

PMID: 29905860

Similar Datasets

Minireview: Signal bias, allosterism, and polymorphic variation at the GLP-1R: implications for drug discovery.

Project description:The glucagon-like peptide-1 receptor (GLP-1R) controls the physiological responses to the incretin hormone glucagon-like peptide-1 and is a major therapeutic target for the treatment of type 2 diabetes, owing to the broad range of effects that are mediated upon its activation. These include the promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of ?-cell mass, improved peripheral insulin action, and promotion of weight loss. Regulation of GLP-1R function is complex, with multiple endogenous and exogenous peptides that interact with the receptor that result in the activation of numerous downstream signaling cascades. The current understanding of GLP-1R signaling and regulation is limited, with the desired spectrum of signaling required for the ideal therapeutic outcome still to be determined. In addition, there are several single-nucleotide polymorphisms (used in this review as defining a natural change of single nucleotide in the receptor sequence; clinically, this is viewed as a single-nucleotide polymorphism only if the frequency of the mutation occurs in 1% or more of the population) distributed within the coding sequence of the receptor protein that have the potential to produce differential responses for distinct ligands. In this review, we discuss the current understanding of GLP-1R function, in particular highlighting recent advances in the field on ligand-directed signal bias, allosteric modulation, and probe dependence and the implications of these behaviors for drug discovery and development.

| S-EPMC3725346 | biostudies-literature

Dynamical allosterism in the mechanism of action of DNA mismatch repair protein MutS.

Project description:The multidomain protein Thermus aquaticus MutS and its prokaryotic and eukaryotic homologs recognize DNA replication errors and initiate mismatch repair. MutS actions are fueled by ATP binding and hydrolysis, which modulate its interactions with DNA and other proteins in the mismatch-repair pathway. The DNA binding and ATPase activities are allosterically coupled over a distance of ?70 Å, and the molecular mechanism of coupling has not been clarified. To address this problem, all-atom molecular dynamics simulations of ?150 ns including explicit solvent were performed on two key complexes--ATP-bound and ATP-free MutS?DNA(+T bulge). We used principal component analysis in fluctuation space to assess ATP ligand-induced changes in MutS structure and dynamics. The molecular dynamics-calculated ensembles of thermally accessible structures showed markedly small differences between the two complexes. However, analysis of the covariance of dynamical fluctuations revealed a number of potentially significant interresidue and interdomain couplings. Moreover, principal component analysis revealed clusters of correlated atomic fluctuations linking the DNA and nucleotide binding sites, especially in the ATP-bound MutS?DNA(+T) complex. These results support the idea that allosterism between the nucleotide and DNA binding sites in MutS can occur via ligand-induced changes in motion, i.e., dynamical allosterism.

| S-EPMC3183814 | biostudies-literature

Sigmoid curves, non-linear double-reciprocal plots and allosterism.

Project description:1. The theory of plane curves was applied to the graphical methods used in enzyme kinetics and a mathematical analysis of the possible graph shapes is given. 2. The belief that allosterism can be inferred from steady-state data alone is subjected to criticism and the mathematical significance of sigmoid curves and non-linear double-reciprocal plots is explored. 3. It is suggested that the usual methods of interpreting steady-state kinetic data are often based on over-restrictive assumptions which prevent maximum utilization of the available data. 4. Methods for obtaining the degree of the rate equation from graph shapes obtained directly from initial-rate measurements and from replots of asymptotic behaviour as chi approach the level 0 and chi approach the level infinity are discussed. 5. Detailed proofs of the theorems given in the text have been deposited as Supplementary Publication SUP 50049 (10 pages) at the British Library (Lending Division), Boston Spa, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1975), 145, 5.

| S-EPMC1165625 | biostudies-other

Direct interdomain interactions can mediate allosterism in the thyroid receptor.

Project description:The thyroid (TR) and retinoid X receptors (RXR) belong to the nuclear receptor (NR) superfamily of ligand-mediated transcription factors. At the molecular level, TR activity is specifically modulated by interactions with the ligand 3,3',5 triiodo-l-thyronine (T3), RXR, DNA, and co-activators such as SRC1, occurring in concert or sequentially. Although binding sites for DNA and coregulators such as SRC1 are distinct and at distal regions of these receptors, cell-based and EMSA studies have suggested that these molecules can regulate binding of each other to the receptor. We present evidence of direct, DNA-dependent, communication between the DNA and ligand binding domains (DBD and LBD) that can allosterically regulate interactions with SRC1 and DNA, respectively, using isothermal titration calorimetry (ITC) and cell-based assays. Additionally, we note that interdomain communication is affected by RXR in RXR:TR. We also noticed a DNA-dependent cross-talk between RXR and TR within RXR:TR. Finally, we suggest that differences in transactivation on different TRE may be the consequence of different affinities between TRE and RXR:TR.

| S-EPMC2755658 | biostudies-literature

Signal integration and information transfer in an allosterically regulated network.

Project description:A biological reaction network may serve multiple purposes, processing more than one input and impacting downstream processes via more than one output. These networks operate in a dynamic cellular environment in which the levels of network components may change within cells and across cells. Recent evidence suggests that protein concentration variability could explain cell fate decisions. However, systems with multiple inputs, multiple outputs, and changing input concentrations have not been studied in detail due to their complexity. Here, we take a systems biochemistry approach, combining physiochemical modeling and information theory, to investigate how cyclooxygenase-2 (COX-2) processes simultaneous input signals within a complex interaction network. We find that changes in input levels affect the amount of information transmitted by the network, as does the correlation between those inputs. This, and the allosteric regulation of COX-2 by its substrates, allows it to act as a signal integrator that is most sensitive to changes in relative input levels.

| S-EPMC6639376 | biostudies-literature

Flavin Charge Transfer Transitions Assist DNA Photolyase Electron Transfer.

Project description:This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH(-)-containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH(-), upon photo-excitation of FADH(-) with 350-450 nm light. We compute the lowest singlet excited states of FADH(-) in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH(-) that is populated after photo-excitation and that acts as the electron donor. For this donor state we compute conformationally-averaged tunneling matrix elements to empty electron- acceptor states of a thymine dimer bound to photolyase. The conformational averaging involves different FADH(-) - thymine dimer confromations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. The tunneling matrix element computations use INDO/S-level Green's function, energy splitting, and Generalized Mulliken-Hush methods. These calculations indicate that photo-excitation of FADH(-) causes a ? ? ?(*) charge-transfer transition that shifts electron density to the side of the flavin isoalloxazine ring that is adjacent to the docked thymine dimer. This shift in electron density enhances the FADH(-) - to - dimer electronic coupling, thus inducing rapid electron transfer.

| S-EPMC3514966 | biostudies-literature

Unraveling a model of TCL/RhoJ allosterism using TC10 reverse chimeras.

Project description:In addition to the classical regulation of GTPase activity by effector proteins, investigating the variations in the amino acid sequence and structures of GTPases often provides insights into regulatory mechanisms that are more GTPase-specific. TCL/RhoJ is a Rho GTPase most closely related to Cdc42 and TC10; however, its nucleotide exchange activity is distinctly influenced by N-terminal amino acids 17-20 and the more distal amino acids 121-129. In this short study, we have further explored the differences between TCL and its homolog TC10 and show that its unique mode of allosteric regulation requires broader diversification of its amino acid sequence than previously appreciated.

| S-EPMC7053938 | biostudies-literature

DNA looping mediates nucleosome transfer.

Project description:Proper cell function requires preservation of the spatial organization of chromatin modifications. Maintenance of this epigenetic landscape necessitates the transfer of parental nucleosomes to newly replicated DNA, a process that is stringently regulated and intrinsically linked to replication fork dynamics. This creates a formidable setting from which to isolate the central mechanism of transfer. Here we utilized a minimal experimental system to track the fate of a single nucleosome following its displacement, and examined whether DNA mechanics itself, in the absence of any chaperones or assembly factors, may serve as a platform for the transfer process. We found that the nucleosome is passively transferred to available dsDNA as predicted by a simple physical model of DNA loop formation. These results demonstrate a fundamental role for DNA mechanics in mediating nucleosome transfer and preserving epigenetic integrity during replication.

| S-EPMC5097161 | biostudies-literature

Micro triboelectric ultrasonic device for acoustic energy transfer and signal communication.

Project description:As a promising energy converter, the requirement for miniaturization and high-accuracy of triboelectric nanogenerators always remains urgent. In this work, a micro triboelectric ultrasonic device was developed by integrating a triboelectric nanogenerator and micro-electro-mechanical systems technology. To date, it sets a world record for the smallest triboelectric device, with a 50?µm-sized diaphragm, and enables the working frequency to be brought to megahertz. This dramatically improves the miniaturization and chip integration of the triboelectric nanogenerator. With 63?kPa@1?MHz ultrasound input, the micro triboelectric ultrasonic device can generate the voltage signal of 16.8?mV and 12.7?mV through oil and sound-attenuation medium, respectively. It also achieved the signal-to-ratio of 20.54?dB and exhibited the practical potential for signal communication by modulating the incident ultrasound. Finally, detailed optimization approaches have also been proposed to further improve the output power of the micro triboelectric ultrasonic device.

| S-EPMC7434882 | biostudies-literature

Transfer functions linking neural calcium to single voxel functional ultrasound signal.

Project description:Functional ultrasound imaging (fUS) is an emerging technique that detects changes of cerebral blood volume triggered by brain activation. Here, we investigate the extent to which fUS faithfully reports local neuronal activation by combining fUS and two-photon microscopy (2PM) in a co-registered single voxel brain volume. Using a machine-learning approach, we compute and validate transfer functions between dendritic calcium signals of specific neurons and vascular signals measured at both microscopic (2PM) and mesoscopic (fUS) levels. We find that transfer functions are robust across a wide range of stimulation paradigms and animals, and reveal a second vascular component of neurovascular coupling upon very strong stimulation. We propose that transfer functions can be considered as reliable quantitative reporters to follow neurovascular coupling dynamics.

| S-EPMC7290037 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data