Allotment of carbon is responsible for disorders in proteins.
Ontology highlight
ABSTRACT:
SUBMITTER: Rajasekaran E
PROVIDER: S-EPMC3134774 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Publications
Allotment of carbon is responsible for disorders in proteins.
Rajasekaran Ekambaram E Akila Kannaiyan K Vijayasarathy Marimuthu M
Bioinformation 20110706 8
Sequence stretches in proteins that do not fold into a form are referred as disordered regions. Databases like Disport describe disordered regions in proteins and web servers like PrDOS and DisEMBL, facilitate the prediction of disordered regions. These studies are often based on residue level features. Here, we describe proteins with disordered regions using carbon content and distributions. The distribution pattern for proteins with disordered regions is different from those that do not show d ...[more]
Similar Datasets
Project description:Background: Perioperative neurocognitive disorders (PND), a postoperative cognitive dysfunction occurs more often in the elderly. The etiology of PND remains largely elusive. This study aims to understand the etiology in a mouse model with tibial fracture (a surgical trauma), by examining the transcriptome-wide response of hippocampus, a brain region that is tightly associated with memory formation. Methods: Mice at age of 7~8 months were randomly divided into two groups, surgery (tibial fracture) group and control (sham) group. At day (d) 1 after the surgical operation, hippocampal tissues were isolated and then subjected to RNA extraction and RNA sequencing (RNA-seq). Findings: Levels of respiratory complex related genes are significantly decreased in the brain of mice subjected to surgery. Consequently, the activities of multiple respiratory complexes and respiratory chain function is decreased in the hippocampus of mice with surgical operation. Interpretation: We here propose a novel mechanism of mitochondrial dysfunction in PND etiology, and also provide a potential therapeutic target for PND.
2022-02-09 | GSE178995 | GEO
Project description:Yeast flocculation is a phenomenon which is believed to result from an interaction between a lectin-like protein and a mannose chain located on the yeast cell surface. The FLO1 gene, which encodes a cell wall protein, is considered to play an important role in yeast flocculation, which is inhibited by mannose but not by glucose (mannose-specific flocculation). A new homologue of FLO1, named Lg-FLO1, was isolated from a flocculent bottom-fermenting yeast strain in which flocculation is inhibited by both mannose and glucose (mannose/glucose-specific flocculation). In order to confirm that both FLO1 and Lg-FLO1 are involved in the yeast flocculation phenomenon, the FLO1 gene in the mannose-specific flocculation strain was replaced by the Lg-FLO1 gene. The transformant in which the Lg-FLO1 gene was incorporated showed the same flocculation phenotype as the mannose/glucose-specific flocculation strain, suggesting that the FLO1 and Lg-FLO1 genes encode mannose-specific and mannose/glucose-specific lectin-like proteins, respectively. Moreover, the sugar recognition sites for these sugars were identified by expressing chimeric FLO1 and Lg-FLO1 genes. It was found that the region from amino acid 196 to amino acid 240 of both gene products is important for flocculation phenotypes. Further mutational analysis of this region suggested that Thr-202 in the Lg-Flo1 protein and Trp-228 in the Flo1 protein are involved in sugar recognition.
| S-EPMC107751 | biostudies-literature
Project description:Perioperative neurocognitive disorders (PNDs) are a type of cognitive dysfunction occurring with a higher incidence in elderly patients. However, the pathological mechanism of PND and effective treatment remain elusive. We generated a PND mouse model by providing wild-type mice with surgical trauma; in our case, we used tibial fracture to investigate PND pathology. Mice aged 7-8 months were randomly divided into two groups: the surgery (tibial fracture) group and the control (sham) group. All mice were subjected to anesthesia. We examined the transcriptome-wide response in the hippocampus, a brain region that is tightly associated with memory formation, of control mice and mice subjected to surgical trauma at day 1 and day 3 after the surgical procedure. We observed reduced transcript levels of respiratory complex components as early as day 1 after surgery, and subsequent protein changes were found at day 3 after surgical trauma. Consequently, the activities of respiratory complexes were reduced, and adenosine triphosphate (ATP) production was decreased in the hippocampus of mice with surgical operations, supporting that respiratory chain function was impaired. In support of these conclusions, the mitochondrial membrane potential (MMP) levels were decreased, and the reactive oxygen species (ROS) levels were significantly increased. Mechanistically, we demonstrated that surgery induced a significant increase in cytokine IL-1β levels at day 1 after surgery, which concomitantly occurred with transcript changes in respiratory complex components. We further uncovered that transcription factors PGC-1α and NRF-1 were responsible for the observed transcript changes in mitochondrial complex components. Importantly, HT22 cells treated with the cytokine IL-1β resulted in similar reductions in PGC-1α and NRF-1, leading to a reduction of both the transcript and protein levels of respiratory complex subunits. Consequently, respiratory function was impaired in HT22 cells treated with IL-1β. Taken together, we demonstrated that reductions in respiratory complex components and subsequent impairment in mitochondrial functions serve as a novel mechanism for PND pathology, providing a potential therapeutic target for PND treatment.
| S-EPMC8865419 | biostudies-literature
Project description:Introduction In recent years, environmental problems such as global warming, rising sea levels, and species extinction have provoked a widespread concern all over the world, and many countries and international organizations have called for a reduction in carbon emissions. Theoretically, although many scholars have explored how responsible leadership influences subordinates’ work-related outcomes, little studies have examined the association between responsible leadership and employees’ low-carbon behavior. Therefore, to address this literature gap, we here drawing upon social cognitive theory developed a dual-mediation model to investigate how responsible leadership impacts employees’ low-carbon behavior, and through which mechanisms this impact may occur. Methods By conducting a questionnaire survey in a company in China, we collected the valid data from 411 samples. Then using SPSS 26.0 and Mplus 8.1, we tested our proposed theoretical model and hypotheses by analyzing these data. Results The empirical results showed that responsible leadership was positively related to employees’ environmental consciousness, which can further increase their low-carbon behavior. At the same time, responsible leadership was negatively related to employees’ environmental apathy, which can reduce their low-carbon behavior. And employees’ environmental consciousness and environmental apathy played the mediating roles in the relationship between responsible leadership and employees’ low-carbon behavior. Furthermore, we found that leader-member exchange (LMX) magnified the direct effect of responsible leadership on employees’ environmental apathy and strengthened the indirect effect of responsible leadership on employees’ low-carbon behavior via environmental apathy, but the moderating effect of LMX on another path was not significant. Discussion These findings suggest that despite encouraging leaders to show responsible behaviors, promoting employees’ environmental consciousness and reducing their environmental apathy may be useful ways to facilitating their low-carbon behavior and achieving a low-carbon society. Moreover, establishing a high-quality of exchange relationship with followers may magnify the effectiveness of responsible leadership on lowering followers’ environmental apathy.
| S-EPMC9869243 | biostudies-literature
Project description:ADAMTS proteins are a superfamily of 26 secreted molecules comprising two related, but distinct families. ADAMTS proteases are zinc metalloendopeptidases, most of whose substrates are extracellular matrix (ECM) components, whereas ADAMTS-like proteins lack a metalloprotease domain, reside in the ECM and have regulatory roles vis-à-vis ECM assembly and/or ADAMTS activity. Evolutionary conservation and expansion of ADAMTS proteins in mammals is suggestive of crucial embryologic or physiological roles in humans. Indeed, Mendelian disorders or birth defects resulting from naturally occurring ADAMTS2, ADAMTS3, ADAMTS10, ADAMTS13, ADAMTS17, ADAMTS20, ADAMTSL2 and ADAMTSL4 mutations as well as numerous phenotypes identified in genetically engineered mice have revealed ADAMTS participation in major biological pathways. Important roles have been identified in a few acquired conditions. ADAMTS5 is unequivocally implicated in pathogenesis of osteoarthritis via degradation of aggrecan, a major structural proteoglycan in cartilage. ADAMTS7 is strongly associated with coronary artery disease and promotes atherosclerosis. Autoantibodies to ADAMTS13 lead to a platelet coagulopathy, thrombotic thrombocytopenic purpura, which is similar to that resulting from ADAMTS13 mutations. ADAMTS proteins have numerous potential connections to other human disorders that were identified by genome-wide association studies. Here, we review inherited and acquired human disorders in which ADAMTS proteins participate, and discuss progress and prospects in therapeutics.
| S-EPMC6146047 | biostudies-literature
Project description:The development of multiple organ dysfunction syndrome (MODS) following infection or tissue injury is associated with increased patient morbidity and mortality. Extensive cellular injury results in the release of nuclear proteins, of which histones are the most abundant, into the circulation. Circulating histones are implicated as essential mediators of MODS. Available anti-histone therapies have failed in clinical trials due to off-target effects such as bleeding and toxicity. Here, we describe a therapeutic strategy for MODS based on the neutralization of histones by chemically stabilized nucleic acid bio-drugs (aptamers). Systematic evolution of ligands by exponential enrichment technology identified aptamers that selectively bind those histones responsible for MODS and do not bind to serum proteins. We demonstrate the efficacy of histone-specific aptamers in human cells and in a murine model of MODS. These aptamers could have a significant therapeutic benefit in the treatment of multiple diverse clinical conditions associated with MODS.
| S-EPMC6328615 | biostudies-literature
Project description:Genipin, a natural compound from Gardenia jasminoides, is a well-known compound in Chinese medicine that is used for the treatment of cancer, inflammation, and diabetes. The use of genipin in classical medicine is hindered because of its unknown molecular mechanisms of action apart from its strong cross-linking ability. Genipin is increasingly applied as a specific inhibitor of proton transport mediated by mitochondrial uncoupling protein 2 (UCP2). However, its specificity for UCP2 is questionable, and the underlying mechanism behind its action is unknown. Here, we investigated the effect of genipin in different systems, including neuroblastoma cells, isolated mitochondria, isolated mitochondrial proteins, and planar lipid bilayer membranes reconstituted with recombinant proteins. We revealed that genipin activated dicarboxylate carrier and decreased the activity of UCP1, UCP3, and complex III of the respiratory chain alongside with UCP2 inhibition. Based on competitive inhibition experiments, the use of amino acid blockers, and site-directed mutagenesis of UCP1, we propose a mechanism of genipin's action on UCPs. At low concentrations, genipin binds to arginine residues located in the UCP funnel, which leads to a decrease in UCP's proton transporting function in the presence of long chain fatty acids. At concentrations above 200 μM, the inhibitory action of genipin on UCPs is overlaid by increased nonspecific membrane conductance due to the formation of protein-genipin aggregates. Understanding the concentration-dependent mechanism of genipin action in cells will allow its targeted application as a drug in the above-mentioned diseases.
| S-EPMC7031773 | biostudies-literature
Project description:We explored the structural features of recombinant ostreolysin A (rOlyA), a protein produced by Pleurotus ostreatus and responsible for binding to α/β-tubulin. We found that rOlyA cell internalization is essential for the induction of adipocyte-associated activity, which is mediated by the interaction of rOlyA and microtubule proteins. We created different point mutations at conserved tryptophan (W) sites in rOlyA and analyzed their biological activity in HIB-1B preadipocytes. We demonstrated that the protein's cell-internalization ability and the differentiated phenotype induced, such as small lipid-droplet formation and gene expression of mitogenesis activity, were impaired in point-mutated proteins W96A and W28A, where W was converted to alanine (A). We also showed that an rOlyA homologue, OlyA6 complexed with mCherry, cannot bind to β-tubulin and does not induce mitochondrial biosynthesis-associated markers, suggesting that the OlyA6 region masked by mCherry is involved in β-tubulin binding. Protein-protein docking simulations were carried out to investigate the binding mode of rOlyA with β-tubulin. Taken together, we identified functional sites in rOlyA that are essential for its binding to β-tubulin and its adipocyte-associated biological activity.
| S-EPMC9598724 | biostudies-literature
Project description:BackgroundCorals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably.Methodology/principal findingsWe screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium.Conclusion/relevanceThis study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.
| S-EPMC3102110 | biostudies-literature
Project description:ZO-1 is a multidomain protein involved in cell-cell junctions and contains three PDZ domains, which are necessary for its function in vivo. PDZ domains play a central role in assembling diverse protein complexes through their ability to recognize short peptide motifs on other proteins. We determined the structure of the second of the three PDZ domains of ZO-1, which is known to promote dimerization as well as bind to C-terminal sequences on connexins. The dimer is stabilized by extensive symmetrical domain swapping of beta-strands, which is unlike any other known mechanism of PDZ dimerization. The canonical peptide-binding groove remains intact in both subunits of the PDZ2 dimer and is created by elements contributed from both monomers. This unique structure reveals an additional example of how PDZ domains dimerize and has multiple implications for both peptide binding and oligomerization in vivo.
| S-EPMC2661428 | biostudies-literature