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ELife Nov 2012Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV)...
Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.DOI:http://dx.doi.org/10.7554/eLife.00049.001.
Topics: Amino Acid Sequence; Animals; Biological Transport; Cell Line; Gene Expression; Hepatitis B virus; Hepatitis Delta Virus; Hepatocytes; Humans; Liver; Molecular Sequence Data; Organic Anion Transporters, Sodium-Dependent; Peptides; Photochemical Processes; Primary Cell Culture; Protein Binding; Protein Structure, Tertiary; Receptors, Virus; Symporters; Taurocholic Acid; Tupaia; Viral Envelope Proteins; Virus Internalization
PubMed: 23150796
DOI: 10.7554/eLife.00049 -
Cancers Nov 2020Dopamine is a biologically active compound belonging to catecholamines. It plays its roles in the human body, acting both as a circulating hormone and neurotransmitter.... (Review)
Review
Dopamine is a biologically active compound belonging to catecholamines. It plays its roles in the human body, acting both as a circulating hormone and neurotransmitter. It acts through G-protein-coupled receptors divided into two subgroups: D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D3R, D4R). Physiologically, dopamine receptors are involved in central nervous system functions: motivation or cognition, and peripheral actions such as blood pressure and immune response modulation. Increasing evidence indicates that the dopamine D1 receptor may play a significant role in developing different human neoplasms. This receptor's value was presented in the context of regulating various signaling pathways important in tumor development, including neoplastic cell proliferation, apoptosis, autophagy, migration, invasiveness, or the enrichment of cancer stem cells population. Recent studies proved that its activation by selective or non-selective agonists is associated with significant tumor growth suppression, metastases prevention, and tumor microvasculature maturation. It may also exert a synergistic anti-cancer effect when combined with tyrosine kinase inhibitors or temozolomide. This review provides a comprehensive insight into the heterogeneity of dopamine D1 receptor molecular roles and signaling pathways in human neoplasm development and discusses possible perspectives of its therapeutic targeting as an adjunct anti-cancer strategy of treatment. We highlight the priorities for further directions in this research area.
PubMed: 33147760
DOI: 10.3390/cancers12113232 -
European Journal of Medical Research Nov 2010Leptin or obesity receptor (Ob-R) is a member of class I cytokine receptor family. Ob-R, expressed in six isoforms, is the product of alternative RNA splicing of db... (Review)
Review
Leptin or obesity receptor (Ob-R) is a member of class I cytokine receptor family. Ob-R, expressed in six isoforms, is the product of alternative RNA splicing of db gene. According to its structural differences, the receptor's isoforms are divided into three classes: long, short, and secretory isoforms. A long, fully active isoform of Ob-Rb is expressed mainly in the hypothalamus, where it takes part in energy homeostasis and in the regulation of secretory organs' activity. Ob-Rb is also present on all types of immune cells, involved in innate and adaptive immunity. Short leptin isoforms (Ob-Ra, Ob-Rc, Ob-Rd, and Ob-Re) that contain box 1 motif are able to bind JAK kinases (Janus kinases) as well as to activate some other signal transduction cascades. A soluble isoform (Ob-Re) can regulate serum leptin concentration and serve as a carrier protein delivering the hormone to its membrane receptors and is able to transduce the signal into the cell. JAK/STAT pathway plays the major role in leptin signal transduction through membrane receptors. Among all Ob-R isoforms, only full-length isoform (Ob-Rb) is able to fully transduce activation signal into the cell.
Topics: Animals; Humans; Polymorphism, Genetic; Receptors, Leptin; Signal Transduction
PubMed: 21147620
DOI: 10.1186/2047-783x-15-s2-50 -
Frontiers in Immunology 2021Plasma membrane provides a biophysical and biochemical platform for immune cells to trigger signaling cascades and immune responses against attacks from foreign... (Review)
Review
Plasma membrane provides a biophysical and biochemical platform for immune cells to trigger signaling cascades and immune responses against attacks from foreign pathogens or tumor cells. Mounting evidence suggests that the biophysical-chemical properties of this platform, including complex compositions of lipids and cholesterols, membrane tension, and electrical potential, could cooperatively regulate the immune receptor functions. However, the molecular mechanism is still unclear because of the tremendous compositional complexity and spatio-temporal dynamics of the plasma membrane. Here, we review the recent significant progress of dynamical regulation of plasma membrane on immune receptors, including T cell receptor, B cell receptor, Fc receptor, and other important immune receptors, to proceed mechano-chemical sensing and transmembrane signal transduction. We also discuss how biophysical-chemical cues couple together to dynamically tune the receptor's structural conformation or orientation, distribution, and organization, thereby possibly impacting their ligand binding and related signal transduction. Moreover, we propose that electrical potential could potentially induce the biophysical-chemical coupling change, such as lipid distribution and membrane tension, to inevitably regulate immune receptor activation.
Topics: Animals; Binding Sites; Cell Membrane; Chemical Phenomena; Electrophysiological Phenomena; Humans; Mechanical Phenomena; Membrane Lipids; Protein Binding; Receptors, Immunologic; Signal Transduction
PubMed: 33679752
DOI: 10.3389/fimmu.2021.613185 -
Journal of Ginseng Research Jan 2017Meyer, belonging to the genus of the family Araliaceae, is known for its human immune system-related effects, such as immune-boosting effects. Ginseng polysaccharides... (Review)
Review
Meyer, belonging to the genus of the family Araliaceae, is known for its human immune system-related effects, such as immune-boosting effects. Ginseng polysaccharides (GPs) are the responsible ingredient of ginseng in immunomodulation, and are classified as acidic and neutral GPs. Although GPs participate in various immune reactions including the stimulation of immune cells and production of cytokines, the precise function of GPs together with its potential receptor(s) and their signal transduction pathways have remained largely unknown. Animal lectins are carbohydrate-binding proteins that are highly specific for sugar moieties. Among many different biological functions , animal lectins especially play important roles in the immune system by recognizing carbohydrates that are found exclusively on pathogens or that are inaccessible on host cells. This review summarizes the immunological activities of GPs and the diverse roles of animal lectins in the immune system, suggesting the possibility of animal lectins as the potential receptor candidates of GPs and giving insights into the development of GPs as therapeutic biomaterials for many immunological diseases.
PubMed: 28123316
DOI: 10.1016/j.jgr.2015.12.006 -
Current Opinion in Structural Biology Dec 2016G protein-coupled receptors (GPCRs) respond to extracellular stimuli and interact with several intracellular binding partners to elicit cellular responses, including... (Review)
Review
G protein-coupled receptors (GPCRs) respond to extracellular stimuli and interact with several intracellular binding partners to elicit cellular responses, including heterotrimeric G proteins. Recent structural and biophysical studies have highlighted the dynamic nature of GPCRs and G proteins and have identified specific conformational changes important for receptor-mediated nucleotide exchange on Gα. While domain separation within Gα is necessary for GDP release, opening the inter-domain interface is insufficient to stimulate nucleotide exchange. Rather, an activated receptor promotes GDP release by allosterically disrupting the nucleotide-binding site via interactions with the Gα N-termini and C-termini. Highlighting the allosteric nature of GPCRs, recent studies suggest that agonist binding alone poorly stabilizes an active conformation of several receptors. Rather, full stabilization of the receptor in an active state requires formation of the agonist-receptor-G protein ternary complex. In turn, nucleotide-free Gα is able to stabilize conformational changes around the receptor's agonist-binding site to enhance agonist affinity.
Topics: Binding Sites; GTP-Binding Proteins; Humans; Nucleotides; Protein Binding; Protein Domains; Receptors, G-Protein-Coupled
PubMed: 27871057
DOI: 10.1016/j.sbi.2016.11.005 -
Biology Jun 2022The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and... (Review)
Review
The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) receptor (also called natriuretic peptide receptor-A (NPR-A)), and C-type natriuretic peptide (CNP), which binds to the GC-B receptor (also called the NPR-B) and then synthesizes intracellular cGMP. GC-A receptor stimulation has natriuretic, vasodilatory, cardiorenal protective and anti-renin-angiotensin-aldosterone system actions, and GC-B receptor stimulation can suppress myocardial fibrosis and can activate bone growth before epiphyseal plate closure. These physiological effects are useful as therapeutics for some disease states, such as heart failure, hypertension, and dwarfism. To optimize the therapeutics for each disease state, we must consider drug metabolism, delivery systems, and target receptor(s). We review the cardiac NP system; new designer NPs, such as modified/combined NPs and modified peptides that can bind to not only NP receptors but receptors for other systems; and oral drugs that enhance endogenous NP activity. Finally, we discuss prospective drug discoveries and the development of novel NP therapeutics.
PubMed: 35741380
DOI: 10.3390/biology11060859 -
Cells Jun 2023The glucocorticoid receptor α (GRα) is a member of the nuclear receptor superfamily and functions as a glucocorticoid (GC)-responsive transcription factor. GR can halt... (Review)
Review
The glucocorticoid receptor α (GRα) is a member of the nuclear receptor superfamily and functions as a glucocorticoid (GC)-responsive transcription factor. GR can halt inflammation and kill off cancer cells, thus explaining the widespread use of glucocorticoids in the clinic. However, side effects and therapy resistance limit GR's therapeutic potential, emphasizing the importance of resolving all of GR's context-specific action mechanisms. Fortunately, the understanding of GR structure, conformation, and stoichiometry in the different GR-controlled biological pathways is now gradually increasing. This information will be crucial to close knowledge gaps on GR function. In this review, we focus on the various domains and mechanisms of action of GR, all from a structural perspective.
Topics: Humans; Glucocorticoids; Receptors, Glucocorticoid; Transcription Factors
PubMed: 37371105
DOI: 10.3390/cells12121636 -
Tropical Medicine and Health Dec 2011Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct...
Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essential for an understanding of dengue pathology. In addition, understanding the molecular mechanism(s) of virus entry is crucial for the development of effective new therapies to treat dengue patients. Binding of dengue virus to its receptor molecules is mediated through a viral envelope glycoprotein, termed E protein. We present a summary and describe the structures, binding properties, and pathological relevance of dengue virus receptor molecules proposed to date. In mammalian cells, there are many candidate molecules that may act as receptors, such as sulfated glycosaminoglycans (GAGs), lectins that recognize carbohydrates, glycosphingolipid (GSL), proteins with chaperone activity, laminin-binding proteins, and other uncharacterized proteins. There are also several lines of evidence for receptor molecules such as GSLs, proteins with chaperone activity, laminin-binding proteins, and other uncharacterized proteins in mosquito cells and organs. This review focuses on several molecules involved in carbohydrate-dependent binding of the virus.
PubMed: 22500135
DOI: 10.2149/tmh.2011-S03