protein interaction

Protein allostery is commonly observed in vitro. But how protein allostery behaves in cells is unknown. In this work, a protein monomer-dimer equilibrium system was built with the allosteric effect on the binding characterized using NMR spectroscopy through mutations away from the dimer interface. A chemical shift linear fitting method was developed that enabled us to accurately determine the dissociation constant. A total of 28 allosteric mutations were prepared and grouped to negative allosteric, nonallosteric, and positive allosteric modulators...

Assemblies of peptides and proteins through specific intermolecular interactions set the basis for macroscopic materials found in nature. Peptides provide easily tunable hydrogen-bonding interactions, which can lead to the formation of ordered structures such as highly stable β-sheets that can form amyloid-like supramolecular peptide nanofibrils (PNFs). PNFs are of special interest, as they could be considered as mimics of various fibrillar structures found in nature. In their ability to serve as supramolecular scaffolds, they could mimic certain features of the extracellular matrix to provide stability, interact with pathogens such as virions, and transduce signals between the outside and inside of cells...

The aggregation of superoxide dismutase 1 (SOD1) results in amyloid deposition and is involved in familial amyotrophic lateral sclerosis, a fatal motor neuron disease. There have been extensive studies of its aggregation mechanism. Noncanonical amino acid 5-cyano-tryptophan (5-CN-Trp), which has been incorporated into the amyloid segments of SOD1 as infrared probes to increase the structural sensitivity of IR spectroscopy, is found to accelerate the overall aggregation rate and potentially modulate the aggregation process...

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase β1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis...

Understanding nanoparticle-cell interaction is essential for advancing research in nanomedicine and nanotoxicology. Apart from the transcytotic pathway mediated by cellular recognition and energetics, nanoparticles (including nanomedicines) may harness the paracellular route for their transport by inducing endothelial leakiness at cadherin junctions. This phenomenon, termed as NanoEL, is correlated with the physicochemical properties of the nanoparticles in close association with cellular signalling, membrane mechanics, as well as cytoskeletal remodelling...

Bone morphogenetic protein 7 (BMP7) can induce skeletal formation, promote the differentiation of chondrocytes and osteoblasts, and ameliorate intervertebral disc degeneration. The study was designed to evaluate the relationship of BMP7 variants to LDH risk in the Chinese Han population. BMP7 variants were genotyped with the Agena MassARRAY system among 690 LDH patients and 690 healthy controls. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression. Multi-factor dimension reduction (MDR) (version 3...

Triatomines (kissing bugs) and tsetse flies (genus: Glossina) are natural vectors of Trypanosoma cruzi and Trypanosoma brucei, respectively. T. cruzi is the causative agent of Chagas disease, endemic in Latin America, while T. brucei causes African sleeping sickness disease in sub-Saharan Africa. Both triatomines and tsetse flies are host to a diverse community of gut microbiota that co-exist with the parasites in the gut. Evidence has shown that the gut microbiota of both vectors plays a key role in parasite development and transmission...

BACKGROUND: The association between dietary protein intake and constipation remains inconclusive. The aim of this study was to investigate whether dietary protein intake is associated with constipation. METHODS: This cross-sectional study included 13,941 adults from the 2005 to 2010 National Health and Nutrition Examination Survey. A weighted logistic regression analysis was used to control for confounding factors. In addition, weighted interaction and stratified analyses were conducted to ascertain the potential modifying factors...

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training...

Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays a key role in the success of European wild rabbit (Oryctolagus cuniculus) and could be affected by the breeding status of the animals and reflected in the metabolome of this species. As nutritional needs are considerably increased during pregnancy and lactation, the main objective of this work was to determine how the breeding status (pregnant and lactating) of European wild rabbit does affects nutritional requirements and their metabolome (using targeted and untargeted metabolomics), aiming to find a useful biomarker of breeding status and for monitoring nutritional requirements...

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versatile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The research of the better part of the cited papers was conducted using various database platforms such as MetalPDB. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life...

Gap junctional connection (GJC) in the cumulus-oocyte complex (COC) provides necessary support for message communication and nutrient transmission required for mammalian oocyte maturation. Cyclic adenosine monophosphate (cAMP) is not only a prerequisite for regulating oocyte meiosis, but also the key intercellular factor for affecting GJC function in COCs. However, there are no reports on whether cAMP regulates connexin 37 (Cx37) expression, one of the main connexin proteins, in sheep COCs. In this study, the expression of Cx37 protein and gene in immature sheep COC was detected using immunohistochemistry and PCR...

Alzheimer's Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD's pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules...

The engineered human cystathionine-γ-lyase (hCGL) resulting in enhanced activity toward both cysteine and cystine unveils a potential robust antitumor activity. However, the presence of cysteine residues has the potential to induce oligomerization or incorrect disulfide bonding, which may decrease the bioavailability of biopharmaceuticals. Through a meticulous design process targeting the cysteine residues within engineered hCGL, a set of potential beneficial mutants were obtained by virtual screening employing Rosetta and ABACUS...

INTRODUCTION: BCL-2 family proteins are important for tumour cell survival and drug resistance in multiple myeloma (MM). Although proteasome inhibitors are effective anti-myeloma drugs, some patients are resistant and almost all eventually relapse. We examined the function of BCL-2 family proteins in stromal-mediated resistance to carfilzomib-induced cytotoxicity in MM cells. METHODS: Co-cultures employing HS5 stromal cells were used to model the interaction with stroma...

Microbial ecosystems experience spatial and nutrient restrictions leading to the coevolution of cooperation and competition among cohabiting species. To increase their fitness for survival, bacteria exploit machinery to antagonizing rival species upon close contact. As such, the bacterial type VI secretion system (T6SS) nanomachinery, typically expressed by pathobionts, can transport proteins directly into eukaryotic or prokaryotic cells, consequently killing cohabiting competitors. Here, we demonstrate for the first time that oral symbiont Aggregatibacter aphrophilus possesses a T6SS and can eliminate its close relative oral pathobiont Aggregatibacter actinomycetemcomitans using its T6SS...

The endoplasmic reticulum (ER) to Golgi secretory pathway is an elegantly complex process whereby protein cargoes are manufactured, folded, and distributed from the ER to the cisternal layers of the Golgi stack before they are delivered to their final destinations. The export of large bulky cargoes such as procollagen and its trafficking to the Golgi is a sophisticated mechanism requiring TANGO1 (Transport ANd Golgi Organization protein 1. It is also called MIA3 (Melanoma Inhibitory Activity protein 3). TANGO1 has two prominent isoforms, TANGO1-Long and TANGO1-Short, and each isoform has specific functions...

We have previously characterized the molecular mechanisms for variants in γ-aminobutyric acid transporter 1-encoding solute carrier family 6-member 1 ( SLC6A1 ) in vitro and concluded that a partial or complete loss of γ-aminobutyric acid uptake due to impaired protein trafficking is the primary aetiology. Impairment of γ-aminobutyric acid transporter 1 function could cause compensatory changes in the expression of γ-aminobutyric acid receptors, which, in turn, modify disease pathophysiology and phenotype...

A cataract is a loss of the transparency of a normal crystalline lens. Multiple factors, including age as the major risk factor for cataracts, can disturb the transparency of the crystalline lens due to cumulative damage from environmental insults to proteins, particularly crystallins. Lens proteins do not turnover, and crystallins undergo extensive post-translational modifications (PTMs) with age in order to interact with each other and maintain their soluble basis for lens transparency. These PTMs include truncation, oxidation, deamidation, acetylation, phosphorylation, and glycosylation...

La protein is significantly expressed in various malignant tumors, including ovarian cancer (OC), which is related to the poor response to platinum-based chemotherapy. Thus, inhibiting La protein could control the expression of the potential downstream genes involved in promoting proliferation and chemotherapy resistance to OC, which could serve as a therapeutic intervention. Through a molecular docking approach, 12 compounds from Morchella esculenta were screened against the crystal structure of La protein and four hit compounds were identified, including beta-carotene, p -hydroxybenzoic acid, gamma-tocopherol, and alpha-tocopherol, with a binding affinity of - 10...