Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Globular and disordered-the non-identical twins in protein-protein interactions.

ABSTRACT: In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1).

SUBMITTER: Teilum K

PROVIDER: S-EPMC4496568 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Globular and disordered-the non-identical twins in protein-protein interactions.

Teilum Kaare K Olsen Johan G JG Kragelund Birthe B BB

Frontiers in molecular biosciences 20150709

In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein in ...[more]

PMID: 26217672

Similar Datasets

INO80 and SWR1 complexes: the non-identical twins of chromatin remodelling.

Project description:The INO80 family of chromatin remodellers are multisubunit complexes that perform a variety of tasks on nucleosomes. Family members are built around a heterohexamer of RuvB-like protein, an ATP-dependent DNA translocase,nuclear actin and actin-related proteins, and a few complex-specific subunits. They modify chromatin in a number of ways including nucleosome sliding and exchange of variant histones. Recent structural information on INO80 and SWR1 complexes has revealed similarities in the basic architecture of the complexes. However, structural and biochemical data on the complexes bound to nucleosomes reveal these similarities to be somewhat superficial and their biochemical activities and mechanisms are very different. Consequently, the INO80 family displays a surprising diversity of function that is based upon a similar structural framework.

| S-EPMC7171469 | biostudies-literature

Adrenal hypoplasia congenita in identical twins.

Project description:We are presenting a monozygotic twin brothers presented at different ages with different presentations. Twin-A presented at age of 18 days with salt losing crisis. Investigations revealed high plasma renin with low-normal aldosterone. Adrenocorticotropic hormone, stimulation test revealed low 17-OH progesterone at 0 and 60 minutes. Adrenocorticotropic hormone level and serum cortisol were normal, which excluded initial impression of congenital adrenal hyperplasia. He was diagnosed to have isolated primary hypoaldosteronism. At age of 18 months, he was noticed to have hyperpigmentation of lips and gum. Adrenal failure was suspected, and hydrocortisone was added. Twin-B presented at 9 years and 6 months of age with adrenal crisis. Both were having unilateral undescended testes. Adrenal hypoplasia congenita (AHC) was suspected after his twin's presentation. Molecular analysis for gene study for both of them revealed adrenal insufficiency, NR0B1 (DAX1) gene mutation. In conclusion, gene analysis is important for the diagnosis of AHC and for genetic counseling.

| S-EPMC6452601 | biostudies-literature

Diffusion-limited association of disordered protein by non-native electrostatic interactions.

Project description:Intrinsically disordered proteins (IDPs) usually fold during binding to target proteins. In contrast to interactions between folded proteins, this additional folding step makes the binding process more complex. Understanding the mechanism of coupled binding and folding of IDPs requires analysis of binding pathways that involve formation of the transient complex (TC). However, experimental characterization of TC is challenging because it only appears for a very brief period during binding. Here, we use single-molecule fluorescence spectroscopy to investigate the mechanism of diffusion-limited association of an IDP. A large enhancement of the association rate is observed due to the stabilization of TC by non-native electrostatic interactions. Moreover, photon-by-photon analysis reveals that the lifetime of TC for IDP binding is at least two orders of magnitude longer than that for binding of two folded proteins. This result suggests the long lifetime of TC is generally required for folding of IDPs during binding processes.

| S-EPMC6226484 | biostudies-literature

Epigenome analysis of female identical twins

Project description:Genome wide DNA methylation profiling of blood samples from eight female identical twins of Han Chinese for forensic age prediction, age 21 to 32. The Illumina Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across approximately 485,000 CpGs at a single-nucleotide resolution. Samples included 8 pairs of identical female twins of Han Chinese.

2015-12-08 | GSE65638 | GEO

Balanced Protein-Water Interactions Improve Properties of Disordered Proteins and Non-Specific Protein Association.

Project description:Some frequently encountered deficiencies in all-atom molecular simulations, such as nonspecific protein-protein interactions being too strong, and unfolded or disordered states being too collapsed, suggest that proteins are insufficiently well solvated in simulations using current state-of-the-art force fields. To address these issues, we make the simplest possible change, by modifying the short-range protein-water pair interactions, and leaving all the water-water and protein-protein parameters unchanged. We find that a modest strengthening of protein-water interactions is sufficient to recover the correct dimensions of intrinsically disordered or unfolded proteins, as determined by direct comparison with small-angle X-ray scattering (SAXS) and Förster resonance energy transfer (FRET) data. The modification also results in more realistic protein-protein affinities, and average solvation free energies of model compounds which are more consistent with experiment. Most importantly, we show that this scaling is small enough not to affect adversely the stability of the folded state, with only a modest effect on the stability of model peptides forming ?-helix and ?-sheet structures. The proposed adjustment opens the way to more accurate atomistic simulations of proteins, particularly for intrinsically disordered proteins, protein-protein association, and crowded cellular environments.

| S-EPMC4230380 | biostudies-literature

Discordant clinical features of identical hypertrophic cardiomyopathy twins.

Project description:Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects ∼1 in 500 individuals and is characterized by increased left ventricular wall thickness. While HCM is caused by pathogenic variants in any one of eight sarcomere protein genes, clinical expression varies considerably, even among patients with the same pathogenic variant. To determine whether background genetic variation or environmental factors drive these differences, we studied disease progression in 11 pairs of monozygotic HCM twins. The twin pairs were followed for 5 to 14 y, and left ventricular wall thickness, left atrial diameter, and left ventricular ejection fraction were collected from echocardiograms at various time points. All nine twin pairs with sarcomere protein gene variants and two with unknown disease etiologies had discordant morphologic features of the heart, demonstrating the influence of nonhereditable factors on clinical expression of HCM. Whole genome sequencing analysis of the six monozygotic twins with discordant HCM phenotypes did not reveal notable somatic genetic variants that might explain their clinical differences. Discordant cardiac morphology of identical twins highlights a significant role for epigenetics and environment in HCM disease progression.

| S-EPMC7958207 | biostudies-literature

Circulating MicroRNAs and Life Expectancy Among Identical Twins.

Project description:Human life expectancy is influenced not only by longevity assurance mechanisms and disease susceptibility loci but also by the environment, gene-environment interactions, and chance. MicroRNAs (miRNAs) are a class of small noncoding RNAs closely related to genes. Circulating miRNAs have been shown as promising noninvasive biomarkers in the development of many pathophysiological conditions. However, the concentration of miRNA in the circulation may also be affected by environmental factors. We used a next-generation sequencing platform to assess the association of circulating miRNA with life expectancy, for which deaths are due to all causes independent of genes. In addition, we showed that miRNAs are present in 41-year archived plasma samples, which may be useful for both life expectancy and all-cause mortality risk assessment. Plasma miRNAs from nine identical male twins were profiled using next-generation sequencing. The average absolute difference in the minimum life expectancy was 9.68 years. Intraclass correlation coefficients were above 0.4 for 50% of miRNAs. Comparing deceased twins with their alive co-twin brothers, the concentrations were increased for 34 but decreased for 30 miRNAs. Identical twins discordant in life expectancy were dissimilar in the majority of miRNAs, suggesting that environmental factors are pivotal in miRNAs related to life expectancy.

| S-EPMC5757377 | biostudies-literature

The human selenoprotein VCP-interacting membrane protein (VIMP) is non-globular and harbors a reductase function in an intrinsically disordered region.

Project description:The human selenoprotein VIMP (VCP-interacting membrane protein)/SelS (selenoprotein S) localizes to the endoplasmic reticulum (ER) membrane and is involved in the process of ER-associated degradation (ERAD). To date, little is known about the presumed redox activity of VIMP, its structure and how these features might relate to the function of the protein in ERAD. Here, we use the recombinantly expressed cytosolic region of VIMP where the selenocysteine (Sec) in position 188 is replaced with a cysteine (a construct named cVIMP-Cys) to characterize redox and structural properties of the protein. We show that Cys-188 in cVIMP-Cys forms a disulfide bond with Cys-174, consistent with the presence of a Cys174-Sec188 selenosulfide bond in the native sequence. For the disulfide bond in cVIMP-Cys we determined the reduction potential to -200 mV, and showed it to be a good substrate of thioredoxin. Based on a biochemical and structural characterization of cVIMP-Cys using analytical gel filtration, CD and NMR spectroscopy in conjunction with bioinformatics, we propose a comprehensive overall structural model for the cytosolic region of VIMP. The data clearly indicate the N-terminal half to be comprised of two extended ?-helices followed by a C-terminal region that is intrinsically disordered. Redox-dependent conformational changes in cVIMP-Cys were observed only in the vicinity of the two Cys residues. Overall, the redox properties observed for cVIMP-Cys are compatible with a function as a reductase, and we speculate that the plasticity of the intrinsically disordered C-terminal region allows the protein to access many different and structurally diverse substrates.

| S-EPMC3406722 | biostudies-literature

Epigenome analysis of female identical twins

2015-12-08 | E-GEOD-65638 | biostudies-arrayexpress

Circulating microRNAs and life expectancy among identical twins

Project description:Objective: To characterize miRNAs in 41-year archived plasma in relation to life expectancy independent of genes. Method: Plasma miRNAs from nine identical male twins were profiled using next-generation sequencing. Results: The average absolute difference in the minimum life expectancy was 9.68 years. Intra-class correlation coefficients were above 0.4 for 50% of miRNAs. Comparing deceased twins with their alive co-twin brothers, the concentrations were increased for 34 but decreased for 30 miRNAs. Conclusion: Identical twins discordant in life expectancy were unlike in the majority of miRNAs, suggesting that environmental factors are pivotal in miRNAs related to life expectancy.

2016-12-30 | GSE80730 | GEO

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