Abstract:
:Molecular determinants of the binding of various endogenous modulators to transient receptor potential (TRP) channels are crucial for the understanding of necessary cellular pathways, as well as new paths for rational drug designs. The aim of this study was to characterise interactions between the TRP cation channel subfamily melastatin member 4 (TRPM4) and endogenous intracellular modulators-calcium-binding proteins (calmodulin (CaM) and S100A1) and phosphatidylinositol 4, 5-bisphosphate (PIP2). We have found binding epitopes at the N- and C-termini of TRPM4 shared by CaM, S100A1 and PIP2. The binding affinities of short peptides representing the binding epitopes of N- and C-termini were measured by means of fluorescence anisotropy (FA). The importance of representative basic amino acids and their combinations from both peptides for the binding of endogenous TRPM4 modulators was proved using point alanine-scanning mutagenesis. In silico protein-protein docking of both peptides to CaM and S100A1 and extensive molecular dynamics (MD) simulations enabled the description of key stabilising interactions at the atomic level. Recently solved cryo-Electron Microscopy (EM) structures made it possible to put our findings into the context of the entire TRPM4 channel and to deduce how the binding of these endogenous modulators could allosterically affect the gating of TRPM4. Moreover, both identified binding epitopes seem to be ideally positioned to mediate the involvement of TRPM4 in higher-order hetero-multimeric complexes with important physiological functions.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Bousova K,Barvik I,Herman P,Hofbauerová K,Monincova L,Majer P,Zouharova M,Vetyskova V,Postulkova K,Vondrasek Jdoi
10.3390/ijms21124323subject
Has Abstractpub_date
2020-06-17 00:00:00issue
12issn
1422-0067pii
ijms21124323journal_volume
21pub_type
杂志文章abstract::Gene fusions have a very important role in the study of cancer development. In this regard, predicting the probability of protein fusion transcripts of developing into a cancer is a very challenging and yet not fully explored research problem. To this date, all the available approaches in literature try to explain the...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20071645
更新日期:2019-04-02 00:00:00
abstract::NASH is becoming increasingly common worldwide because of the growing global prevalence of obesity and consequently NAFLD. Unfortunately, the mechanism of progression of NAFLD to NASH and then cirrhosis is not completely understood. Several factors, including insulin resistance, inflammation, oxidative stress, lipotox...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19072034
更新日期:2018-07-13 00:00:00
abstract::Sleep remains one of the least understood phenomena in biology, and sleep disturbances are one of the most common behavioral problems in childhood. The etiology of sleep disorders is complex and involves both genetic and environmental factors. Epilepsy is the most popular childhood neurological condition and is charac...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20215483
更新日期:2019-11-04 00:00:00
abstract::The cause of inflammatory bowel disease (IBD) is still unknown, but there is growing evidence that environmental factors such as epigenetic changes can contribute to the disease etiology. The aim of this study was to identify newly hypermethylated genes in ulcerative colitis (UC) using a genome-wide DNA methylation ap...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17081291
更新日期:2016-08-09 00:00:00
abstract::Integration of multiple sources and data levels provides a great insight into the complex associations between human and malaria systems. In this study, a meta-analysis framework was developed based on a heterogeneous network model for integrating human-malaria protein similarities, a human protein interaction network...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21041310
更新日期:2020-02-15 00:00:00
abstract::The human peptide GHK (glycyl-l-histidyl-l-lysine) has multiple biological actions, all of which, according to our current knowledge, appear to be health positive. It stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis, as well as supports the function of dermal fi...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19071987
更新日期:2018-07-07 00:00:00
abstract::Mesenchymal stem cells (MSCs) are considered as promising therapeutic agents for neurodegenerative disorders because they can reduce underlying pathology and also repair damaged tissues. Regarding the delivery of MSCs into the brain, intravenous and intra-arterial routes may be less feasible than intraparenchymal and ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21041272
更新日期:2020-02-13 00:00:00
abstract::Recent studies have shown that free fatty acids are associated with chronic inflammation, which may be involved in vascular injury. The intake of eicosapentaenoic acid (EPA) can decrease cardiovascular disease risks, but the protective mechanisms of EPA on endothelial cells remain unclear. In this study, primary human...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms150610334
更新日期:2014-06-10 00:00:00
abstract::Neurodegenerative disorders affect around one billion people worldwide. They can arise from a combination of genomic, epigenomic, metabolic, and environmental factors. Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer's and Parkinson's diseases. A progressive neurodegenerative...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20030719
更新日期:2019-02-08 00:00:00
abstract::Civilization diseases associated with memory disorders are important health problems occurring due to a prolonged life span. The manuscript shows the results of an in vivo study targeting the emergence of two drug candidates with anti-amnestic properties. The preceding quantitative structure-activity relationship (QSA...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18122511
更新日期:2017-11-24 00:00:00
abstract::Regulation of synaptically located ionotropic receptors is thought to be the main mechanism by which anaesthetics cause unconsciousness. An alternative explanation, which has received much less attention, is that of primary anaesthetic disruption of brain metabolism via suppression of mitochondrial proteins. In this p...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21134703
更新日期:2020-07-01 00:00:00
abstract::The surface attachment properties of the Creutz-Taube ion, i.e., [(NH(3))(5)Ru(pyrazine)Ru(NH(3))(5)](5+), on both hydrophilic and hydrophobic types of surfaces were investigated using X-ray photoelectron spectroscopy (XPS). The results indicated that the Creutz-Taube ions only bound to hydrophilic surfaces, such as S...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms10020533
更新日期:2009-02-01 00:00:00
abstract::It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inf...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20010169
更新日期:2019-01-04 00:00:00
abstract::Vitamin D deficiency is the most common nutritional deficiency, affecting almost one billion people worldwide. Vitamin D is mostly known for its role in intestinal calcium absorption and bone mineralization. However, the observation of seasonal changes in blood pressure and the subsequent identification of vitamin D r...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21186483
更新日期:2020-09-04 00:00:00
abstract::Chronic infection with hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC). Novel treatments with direct-acting antivirals achieve high rates of sustained virologic response; however, the HCC risk remains elevated in cured patients, especially those with advanced liver disease. Long-term HCV inf...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21093057
更新日期:2020-04-26 00:00:00
abstract::Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especiall...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21041392
更新日期:2020-02-19 00:00:00
abstract::Alzheimer's disease is believed to begin with synaptic dysfunction caused by soluble Aβ oligomers. When this oligomer hypothesis was proposed in 2002, there was no direct evidence that Aβ oligomers actually disrupt synaptic function to cause cognitive impairment in humans. In patient brains, both soluble and insoluble...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21041413
更新日期:2020-02-19 00:00:00
abstract::Catalytic decomposition of sucrose by acid invertases (AINVs) under acidic conditions plays an important role in the development of sink organs in plants. To reveal the function of AINVs in the development of pepper fruits, nine AINV genes of pepper were identified. Protein sequencing and phylogenetic analysis reveale...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20010015
更新日期:2018-12-20 00:00:00
abstract::Rhodobactersphaeroides has two chemotaxis clusters, an Escherichia coli-like cluster with membrane-spanning chemoreceptors and a less-understood cytoplasmic cluster. The cytoplasmic CheA is split into CheA4, a kinase, and CheA3, a His-domain phosphorylated by CheA4 and a phosphatase domain, which together phosphorylat...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20205095
更新日期:2019-10-14 00:00:00
abstract::Apoptosis, also called programmed cell death, is an orderly cellular suicide program that is critical for the development, immune regulation and homeostasis of a multi-cellular organism. Failure to control this process can lead to serious human diseases, including many types of cancer, neurodegenerative diseases, and ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms13044807
更新日期:2012-01-01 00:00:00
abstract::To design ARC-111 analogues with improved efficiency, we constructed the QSAR of 22 ARC-111 analogues with RPMI8402 tumor cells. First, the optimized support vector regression (SVR) model based on the literature descriptors and the worst descriptor elimination multi-roundly (WDEM) method had similar generalization as ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13011161
更新日期:2012-01-01 00:00:00
abstract::Dietary supplementation with polyunsaturated fatty acids (PUFA) n-3 can affect cutaneous wound healing; however, recent findings demonstrate the variable extent of their influence on the quality of healing. Here, we compare the effect of several dietary oils, containing different levels of PUFA n-3 and PUFA n-6, on wo...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21217911
更新日期:2020-10-24 00:00:00
abstract::Deficits in plasma membrane repair have been identified in dysferlinopathy and Duchenne Muscular Dystrophy, and contribute to progressive myopathy. Although Facioscapulohumeral Muscular Dystrophy (FSHD) shares clinicopathological features with these muscular dystrophies, it is unknown if FSHD is characterized by plasm...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21155575
更新日期:2020-08-04 00:00:00
abstract::Octamer-binding transcription factor 4 (Oct4) is a member of POU (Pit-Oct-Unc) transcription factor family Class V that plays a crucial role in maintaining the pluripotency and self-renewal of stem cells. Though it has been deeply investigated in mammals, its lower vertebrate homologue, especially in the marine fish, ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18010231
更新日期:2017-01-23 00:00:00
abstract::Benzimidazole derivatives have a diverse range of biological activities, including antiulcer, antihypertensive, antiviral, antifungal, anti-inflammatory, and anticancer. Despite these activities, previous studies have revealed that some of the derivatives can induce mutations. This study aimed to screen for potential ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20184324
更新日期:2019-09-04 00:00:00
abstract::The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in estab...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms17040593
更新日期:2016-04-19 00:00:00
abstract::Adiponectin (ApN) is a hormone abundantly secreted by adipocytes and it is known to be tightly linked to the metabolic syndrome. It promotes insulin-sensitizing, fat-burning, and anti-atherosclerotic actions, thereby effectively counteracting several metabolic disorders, including type 2 diabetes, obesity, and cardiov...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21072620
更新日期:2020-04-09 00:00:00
abstract::Ostrinia furnacalis, is the major pest of maize causing significant yield losses. So far, many approaches have been used to increase the virulence of entomopathogenic fungal isolates. The current study is an attempt to estimate synergistic effect of Beauveria bassiana and Trichoderma asperellum in order to explore lar...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21218215
更新日期:2020-11-03 00:00:00
abstract::In order to determine the effect of different gelation temperatures (80 °C and 90 °C) on the structural arrangements in 1,3-β-d-glucan (curdlan) matrices, spectroscopic and microscopic approaches were chosen. Attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) and Raman spectroscopy are wel...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21176154
更新日期:2020-08-26 00:00:00
abstract::Vasoactive intestinal peptide receptor 1 (VPAC1) is a member of a secretin-like subfamily of G protein-coupled receptors. Its endogenous neuropeptide (VIP), secreted by neurons and immune cells, modulates various physiological functions such as exocrine and endocrine secretions, immune response, smooth muscles relaxat...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20184348
更新日期:2019-09-05 00:00:00