Base de dados : MEDLINE
Pesquisa : D12.776.157.530.400.400.100 [Categoria DeCS]
Referências encontradas : 50 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 5 ir para página              

  1 / 50 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28606760
[Au] Autor:Sparling BA; DiMauro EF
[Ad] Endereço:Department of Medicinal Chemistry, Amgen Inc., 360 Binney Street, Cambridge, MA 02142, USA.
[Ti] Título:Progress in the discovery of small molecule modulators of the Cys-loop superfamily receptors.
[So] Source:Bioorg Med Chem Lett;27(15):3207-3218, 2017 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The vertebrate Cys-loop family of ligand-gated ion channels (LGICs) are comprised of nicotinic acetylcholine (nAChR), serotonin type 3 (5-HT R), γ-aminobutyric acid (GABA R), and glycine (GlyR) receptors. Here, we review efforts to discover selective small molecules targeting one or more Cys-loop receptors, with a focus on state-of-the-art modulators that have been reported over the past five years. Several highlighted compounds offer robust oral bioavailability and central exposure and have thus been useful in delineating pharmacokinetic/pharmacodynamic relationships in pre-clinical disease models. Others offer high levels of subtype and/or inter-superfamily selectivity and have facilitated understanding of complex SAR and pharmacodynamics.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/agonistas
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/antagonistas & inibidores
Bibliotecas de Moléculas Pequenas/química
Bibliotecas de Moléculas Pequenas/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Disponibilidade Biológica
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Descoberta de Drogas
Seres Humanos
Modelos Moleculares
Bibliotecas de Moléculas Pequenas/administração & dosagem
Bibliotecas de Moléculas Pequenas/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Small Molecule Libraries)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE


  2 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28146602
[Au] Autor:Nicholl GC; Jawad AK; Weymouth R; Zhang H; Beg AA
[Ad] Endereço:Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
[Ti] Título:Pharmacological characterization of the excitatory 'Cys-loop' GABA receptor family in Caenorhabditis elegans.
[So] Source:Br J Pharmacol;174(9):781-795, 2017 May.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Ionotropic GABA receptors are evolutionarily conserved proteins that mediate cellular and network inhibition in both vertebrates and invertebrates. A unique class of excitatory GABA receptors has been identified in several nematode species. Despite well-characterized functions in Caenorhabditis elegans, little is known about the pharmacology of the excitatory GABA receptors EXP-1 and LGC-35. Using a panel of compounds that differentially activate and modulate ionotropic GABA receptors, we investigated the agonist binding site and allosteric modulation of EXP-1 and LGC-35. EXPERIMENTAL APPROACH: We used two-electrode voltage clamp recordings to characterize the pharmacological profile of EXP-1 and LGC-35 receptors expressed in Xenopus laevis oocytes. KEY RESULTS: The pharmacology of EXP-1 and LGC-35 is different from that of GABA and GABA -ρ receptors. Both nematode receptors are resistant to the competitive orthosteric antagonist bicuculline and to classical ionotropic receptor pore blockers. The GABA -ρ specific antagonist, TPMPA, was the only compound tested that potently inhibited EXP-1 and LGC-35. Neurosteroids have minimal effects on GABA-induced currents, but ethanol selectively potentiates LGC-35. CONCLUSIONS AND IMPLICATIONS: The pharmacological properties of EXP-1 and LGC-35 more closely resemble the ionotropic GABA -ρ family. However, EXP-1 and LGC-35 exhibit a unique profile that differs from vertebrate GABA and GABA -ρ receptors, insect GABA receptors and nematode GABA receptors. As a pair, EXP-1 and LGC-35 may be utilized to further understand the differential molecular mechanisms of agonist, antagonist and allosteric modulation at ionotropic GABA receptors and may aid in the design of new and more specific anthelmintics that target GABA neurotransmission.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/agonistas
Proteínas de Caenorhabditis elegans/metabolismo
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/agonistas
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Receptores de GABA/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/fisiologia
Caenorhabditis elegans
Proteínas de Caenorhabditis elegans/genética
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/genética
Relação Dose-Resposta a Droga
Feminino
Agonistas GABAérgicos/metabolismo
Agonistas GABAérgicos/farmacologia
Receptores de GABA/genética
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (EXP-1 protein, C elegans); 0 (GABA Agonists); 0 (LGC-35 protein, C elegans); 0 (Receptors, GABA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170202
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13736


  3 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27650259
[Au] Autor:Liu H; French AS; Torkkeli PH
[Ad] Endereço:Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.
[Ti] Título:Expression of Cys-loop receptor subunits and acetylcholine binding protein in the mechanosensory neurons, glial cells, and muscle tissue of the spider Cupiennius salei.
[So] Source:J Comp Neurol;525(5):1139-1154, 2017 Apr 01.
[Is] ISSN:1096-9861
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The central and peripheral nervous system transcriptomes of the spider Cupiennius salei have 15 Cys-loop receptor subunits and an acetylcholine-binding protein (AChBP). Twelve subunits are predicted to form anion channels gated by γ-aminobutyric acid (GABA), glutamate, histamine, or changes in pH, and three are putative ACh-gated cation channels. Spiders have a variety of mechanosensilla and proprioceptive organs that are innervated by efferents in their peripherally located parts, and efferents also innervate muscle fibers. We investigated Cys-loop gene expression in muscle tissue by qPCR and localized this expression in mechanosensilla via in situ hybridization. The cuticular mechanosensory neurons had only CsGABArdl and CspHCl2 subunits, whereas the muscle tissue expressed a wider variety of subunits, especially CsGABAgrd, CsGABA ß, CsGluCl1 and CspHCl, but very low levels of the CsGABArdl or CsnACh subunits. An nACh non-α subunit was expressed in a group of unidentified cells in the hypodermis and at low level in the muscle tissue, but the physiological function of this subunit is unknown. The CsnAChα subunit was not expressed in sensory neurons and was expressed at extremely low level in the muscle tissue. None of the probes gave signals in proprioceptive joint receptors, suggesting that efferent innervation to this sense organ employs other receptor types. CsAChBP and a glia-specific homeodomain CsREPO were both expressed in glial cells that surround sensory neurons and also in muscle tissue, probably around the nerve endings of the neuromuscular junction. These locations have large numbers of synapses, suggesting that AChBP may have a function in modulating synaptic transmission. J. Comp. Neurol. 525:1139-1154, 2017. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/biossíntese
Mecanorreceptores/metabolismo
Músculo Esquelético/metabolismo
Neuroglia/metabolismo
Aranhas/fisiologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Imuno-Histoquímica
Hibridização In Situ
Mecanotransdução Celular/fisiologia
Microscopia Eletrônica de Transmissão
Reação em Cadeia da Polimerase
Sensilas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160922
[St] Status:MEDLINE
[do] DOI:10.1002/cne.24122


  4 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27417718
[Au] Autor:Faure G; Shelukhina IV; Porowinska D; Shulepko MA; Lyukmanova EN; Dolgikh DA; Spirova EN; Kasheverov IE; Utkin YN; Corringer JP; Tsetlin VI
[Ad] Endereço:Pasteur Institute, Paris, France. ner-neri@yandex.ru.
[Ti] Título:Interaction of three-finger proteins from snake venoms and from mammalian brain with the cys-loop receptors and their models.
[So] Source:Dokl Biochem Biophys;468(1):193-6, 2016 May.
[Is] ISSN:1608-3091
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:With the use of surface plasmon resonance (SPR) it was shown that ws-Lynx1, a water-soluble analog of the three-finger membrane-bound protein Lynx1, that modulates the activity of brain nicotinic acetylcholine receptors (nAChRs), interacts with the acetylcholine-binding protein (AChBP) with high affinity, K D = 62 nM. This result agrees with the earlier demonstrated competition of ws-Lynx1 with radioiodinated α-bungarotoxin for binding to AChBP. For the first time it was shown that ws-Lynx1 binds to GLIC, prokaryotic Cys-loop receptor (K D = 1.3 µM). On the contrary, SPR revealed that α-cobratoxin, a three-finger protein from cobra venom, does not bind to GLIC. Obtained results indicate that SPR is a promising method for analysis of topography of ws-Lynx1 binding sites using its mutants and those of AChBP and GLIC.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Encéfalo/metabolismo
Proteínas Neurotóxicas de Elapídeos/metabolismo
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Glicoproteínas de Membrana/metabolismo
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Mh] Termos MeSH secundário: Animais
Aplysia
Proteínas de Bactérias/química
Sítios de Ligação
Linhagem Celular
Linhagem Celular Tumoral
Cianobactérias
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química
Drosophila melanogaster
Venenos Elapídicos/química
Venenos Elapídicos/metabolismo
Elapidae
Escherichia coli
Células HEK293
Seres Humanos
Glicoproteínas de Membrana/química
Glicoproteínas de Membrana/genética
Modelos Moleculares
Estrutura Secundária de Proteína
Ressonância de Plasmônio de Superfície
Receptor Nicotínico de Acetilcolina alfa7/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cobra Neurotoxin Proteins); 0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Elapid Venoms); 0 (Membrane Glycoproteins); 0 (Naja kaouthia venom); 0 (alpha7 Nicotinic Acetylcholine Receptor); 69344-74-7 (alpha-cobratoxin)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160716
[St] Status:MEDLINE
[do] DOI:10.1134/S1607672916030091


  5 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27273633
[Au] Autor:Plested AJ
[Ad] Endereço:Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany.
[Ti] Título:Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels.
[So] Source:Nat Struct Mol Biol;23(6):494-502, 2016 Jun 07.
[Is] ISSN:1545-9985
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ion channels gated by neurotransmitters are present across metazoans, in which they are essential for brain function, sensation and locomotion; closely related homologs are also found in bacteria. Structures of eukaryotic pentameric cysteine-loop (Cys-loop) receptors and tetrameric ionotropic glutamate receptors in multiple functional states have recently become available. Here, I describe how these studies relate to established ideas regarding receptor activation and how they have enabled decades' worth of functional work to be pieced together, thus allowing previously puzzling aspects of receptor activity to be understood.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química
Canais Iônicos/química
Neurotransmissores/metabolismo
Receptores de Glutamato/química
Sinapses/metabolismo
Transmissão Sináptica/fisiologia
[Mh] Termos MeSH secundário: Animais
Bactérias/química
Bactérias/metabolismo
Benzotiadiazinas/farmacologia
Cognição/efeitos dos fármacos
Cognição/fisiologia
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/genética
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Expressão Gênica
Seres Humanos
Ativação do Canal Iônico/efeitos dos fármacos
Canais Iônicos/genética
Canais Iônicos/metabolismo
Ivermectina/farmacologia
Locomoção/efeitos dos fármacos
Locomoção/fisiologia
Modelos Moleculares
Percepção/efeitos dos fármacos
Percepção/fisiologia
Piperidinas/farmacologia
Receptores de Glutamato/genética
Receptores de Glutamato/metabolismo
Sinapses/efeitos dos fármacos
Transmissão Sináptica/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Benzothiadiazines); 0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Ion Channels); 0 (Neurotransmitter Agents); 0 (Piperidines); 0 (Receptors, Glutamate); 70288-86-7 (Ivermectin); P71U09G5BW (cyclothiazide); R8OE3P6O5S (ifenprodil)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170607
[Lr] Data última revisão:
170607
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE
[do] DOI:10.1038/nsmb.3214


  6 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26999666
[Au] Autor:Wijckmans E; Nys M; Debaveye S; Brams M; Pardon E; Willegems K; Bertrand D; Steyaert J; Efremov R; Ulens C
[Ad] Endereço:Department of Cellular and Molecular Medicine, Laboratory of Structural Neurobiology, University of Leuven, Leuven, Belgium.
[Ti] Título:Functional and Biochemical Characterization of Alvinella pompejana Cys-Loop Receptor Homologues.
[So] Source:PLoS One;11(3):e0151183, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cys-loop receptors are membrane spanning ligand-gated ion channels involved in fast excitatory and inhibitory neurotransmission. Three-dimensional structures of these ion channels, determined by X-ray crystallography or electron microscopy, have revealed valuable information regarding the molecular mechanisms underlying ligand recognition, channel gating and ion conductance. To extend and validate the current insights, we here present promising candidates for further structural studies. We report the biochemical and functional characterization of Cys-loop receptor homologues identified in the proteome of Alvinella pompejana, an extremophilic, polychaete annelid found in hydrothermal vents at the bottom of the Pacific Ocean. Seven homologues were selected, named Alpo1-7. Five of them, Alpo2-6, were unidentified prior to this study. Two-electrode voltage clamp experiments revealed that wild type Alpo5 and Alpo6, both sharing remarkably high sequence identity with human glycine receptor α subunits, are anion-selective channels that can be activated by glycine, GABA and taurine. Furthermore, upon expression in insect cells fluorescence size-exclusion chromatography experiments indicated that four homologues, Alpo1, Alpo4, Alpo6 and Alpo7, can be extracted out of the membrane by a wide variety of detergents while maintaining their oligomeric state. Finally, large-scale purification efforts of Alpo1, Alpo4 and Alpo6 resulted in milligram amounts of biochemically stable and monodisperse protein. Overall, our results establish the evolutionary conservation of glycine receptors in annelids and pave the way for future structural studies.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Poliquetos/metabolismo
Homologia de Sequência de Aminoácidos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/isolamento & purificação
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/ultraestrutura
Glicina/farmacologia
Proteínas de Fluorescência Verde/metabolismo
Íons
Ligantes
Dados de Sequência Molecular
Multimerização Proteica
Estabilidade Proteica
Subunidades Proteicas/química
Subunidades Proteicas/metabolismo
Proteoma/metabolismo
Análise de Sequência de Proteína
Anticorpos de Domínio Único/metabolismo
Taurina/farmacologia
Temperatura Ambiente
Ácido gama-Aminobutírico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Ions); 0 (Ligands); 0 (Protein Subunits); 0 (Proteome); 0 (Single-Domain Antibodies); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); 1EQV5MLY3D (Taurine); 56-12-2 (gamma-Aminobutyric Acid); TE7660XO1C (Glycine)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160324
[Lr] Data última revisão:
160324
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160322
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0151183


  7 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26986966
[Au] Autor:Jaiteh M; Taly A; Hénin J
[Ad] Endereço:Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, CNRS and Université Paris Diderot, Paris, France.
[Ti] Título:Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors.
[So] Source:PLoS One;11(3):e0151934, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pentameric ligand-gated ion channels (pLGICs) are ubiquitous neurotransmitter receptors in Bilateria, with a small number of known prokaryotic homologues. Here we describe a new inventory and phylogenetic analysis of pLGIC genes across all kingdoms of life. Our main finding is a set of pLGIC genes in unicellular eukaryotes, some of which are metazoan-like Cys-loop receptors, and others devoid of Cys-loop cysteines, like their prokaryotic relatives. A number of such "Cys-less" receptors also appears in invertebrate metazoans. Together, those findings draw a new distribution of pLGICs in eukaryotes. A broader distribution of prokaryotic channels also emerges, including a major new archaeal taxon, Thaumarchaeota. More generally, pLGICs now appear nearly ubiquitous in major taxonomic groups except multicellular plants and fungi. However, pLGICs are sparsely present in unicellular taxa, suggesting a high rate of gene loss and a non-essential character, contrasting with their essential role as synaptic receptors of the bilaterian nervous system. Multiple alignments of these highly divergent sequences reveal a small number of conserved residues clustered at the interface between the extracellular and transmembrane domains. Only the "Cys-loop" proline is absolutely conserved, suggesting the more fitting name "Pro loop" for that motif, and "Pro-loop receptors" for the superfamily. The infered molecular phylogeny shows a Cys-loop and a Cys-less clade in eukaryotes, both containing metazoans and unicellular members. This suggests new hypotheses on the evolutionary history of the superfamily, such as a possible origin of the Cys-loop cysteines in an ancient unicellular eukaryote. Deeper phylogenetic relationships remain uncertain, particularly around the split between bacteria, archaea, and eukaryotes.
[Mh] Termos MeSH primário: Canais Iônicos de Abertura Ativada por Ligante/genética
Receptores de Neurotransmissores/genética
[Mh] Termos MeSH secundário: Animais
Archaea/classificação
Archaea/genética
Archaea/fisiologia
Sequência Conservada/genética
Sequência Conservada/fisiologia
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/genética
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/fisiologia
Eucariotos/genética
Eucariotos/fisiologia
Evolução Molecular
Fungos/genética
Fungos/fisiologia
Invertebrados/genética
Invertebrados/fisiologia
Canais Iônicos de Abertura Ativada por Ligante/fisiologia
Filogenia
Plantas/genética
Receptores de Neurotransmissores/fisiologia
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Ligand-Gated Ion Channels); 0 (Receptors, Neurotransmitter)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160318
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0151934


  8 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26920686
[Au] Autor:Fu YL; Wang YJ; Mu TW
[Ad] Endereço:Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
[Ti] Título:Proteostasis Maintenance of Cys-Loop Receptors.
[So] Source:Adv Protein Chem Struct Biol;103:1-23, 2016.
[Is] ISSN:1876-1623
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The Cys-loop receptors play prominent roles in the nervous system. They include γ-aminobutyric acid type A receptors, nicotinic acetylcholine receptors, 5-hydroxytryptamine type-3 receptors, and glycine receptors. Proteostasis represents an optimal state of the cellular proteome in normal physiology. The proteostasis network regulates the folding, assembly, degradation, and trafficking of the Cys-loop receptors, ensuring their efficient functional cell surface expressions. Here, we summarize current advances about the protein biogenesis process of the Cys-loop receptors. Because operating on individual biogenesis steps influences the receptor cell surface level, manipulating the proteostasis network components can regulate the function of the receptors, representing an emerging therapeutic strategy for corresponding channelopathies.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química
Receptores de GABA/química
Receptores da Glicina/química
Receptores Nicotínicos/química
Receptores 5-HT3 de Serotonina/química
[Mh] Termos MeSH secundário: Membrana Celular
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Endocitose/genética
Retículo Endoplasmático/química
Retículo Endoplasmático/metabolismo
Complexo de Golgi/química
Complexo de Golgi/metabolismo
Dobramento de Proteína
Transporte Proteico/genética
Receptores de GABA/metabolismo
Receptores da Glicina/metabolismo
Receptores Nicotínicos/metabolismo
Receptores 5-HT3 de Serotonina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Receptors, GABA); 0 (Receptors, Glycine); 0 (Receptors, Nicotinic); 0 (Receptors, Serotonin, 5-HT3)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160227
[Lr] Data última revisão:
160227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160228
[St] Status:MEDLINE


  9 / 50 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26381939
[Au] Autor:Akabas MH
[Ad] Endereço:Departments of Physiology & Biophysics, Neuroscience and Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461, Bronx, NY, USA. myles.akabas@einstein.yu.edu.
[Ti] Título:Cysteine Modification: Probing Channel Structure, Function and Conformational Change.
[So] Source:Adv Exp Med Biol;869:25-54, 2015.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cysteine substitution has been a powerful tool to investigate the structure and function of proteins. It has been particularly useful for studies of membrane proteins in their native environment, embedded in phospholipid membranes. Among the 20 amino acids, cysteine is uniquely reactive. This reactivity has motivated the synthesis of a wide array of sulfhydryl reactive chemicals. The commercially available array of sulfhydryl reactive reagents has allowed investigators to probe the local steric and electrostatic environment around engineered cysteines and to position fluorescent, paramagnetic and mass probes at specific sites within proteins and for distance measurements between pairs of sites. Probing the reactivity and accessibility of engineered cysteines has been extensively used in Substituted Cysteine Accessibility Method (SCAM) investigations of ion channels, membrane transporters and receptors. These studies have successfully identified the residues lining ion channels, agonist/antagonist and allosteric modulator binding sites, and regions whose conformation changes as proteins transition between different functional states. The thousands of cysteine-substitution mutants reported in the literature demonstrate that, in general, mutation to cysteine is well tolerated. This has allowed systematic studies of residues in transmembrane segments and in other parts of membrane proteins. Finally, by inserting pairs of cysteines and assaying their ability to form disulfide bonds, changes in proximity and mobility relationships between specific positions within a protein can be inferred. Thus, cysteine mutagenesis has provided a wealth of data on the structure of membrane proteins in their functional environment. This data can complement the structural insights obtained from the burgeoning number of crystal structures of detergent solubilized membrane proteins whose functional state is often uncertain. This article will review the use of cysteine mutagenesis to probe structure-function relationships in ion channels focusing mainly on Cys-loop receptors.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Ativação do Canal Iônico
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Cisteína
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/genética
Seres Humanos
Transporte de Íons
Ligantes
Potenciais da Membrana
Modelos Químicos
Mutagênese Sítio-Dirigida
Mutação
Ligação Proteica
Conformação Proteica
Substâncias Redutoras/química
Eletricidade Estática
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Ligands); 0 (Reducing Agents); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:161109
[Lr] Data última revisão:
161109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150919
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-2845-3_3


  10 / 50 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25891813
[Au] Autor:Gielen M; Thomas P; Smart TG
[Ad] Endereço:Department of Neuroscience, Physiology &Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
[Ti] Título:The desensitization gate of inhibitory Cys-loop receptors.
[So] Source:Nat Commun;6:6829, 2015 Apr 20.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cys-loop neurotransmitter-gated ion channels are vital for communication throughout the nervous system. Following activation, these receptors enter into a desensitized state in which the ion channel shuts even though the neurotransmitter molecules remain bound. To date, the molecular determinants underlying this most fundamental property of Cys-loop receptors have remained elusive. Here we present a generic mechanism for the desensitization of Cys-loop GABAA (GABAARs) and glycine receptors (GlyRs), which both mediate fast inhibitory synaptic transmission. Desensitization is regulated by interactions between the second and third transmembrane segments, which affect the ion channel lumen near its intracellular end. The GABAAR and GlyR pore blocker picrotoxin prevented desensitization, consistent with its deep channel-binding site overlapping a physical desensitization gate.
[Mh] Termos MeSH primário: Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo
Ativação do Canal Iônico/fisiologia
Receptores da Glicina/metabolismo
[Mh] Termos MeSH secundário: Animais
Clonagem Molecular
Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/genética
Regulação da Expressão Gênica/fisiologia
Células HEK293
Seres Humanos
Cinética
Camundongos
Modelos Biológicos
Modelos Moleculares
Oócitos
Conformação Proteica
Subunidades Proteicas
Receptores da Glicina/genética
Proteínas Recombinantes
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cysteine Loop Ligand-Gated Ion Channel Receptors); 0 (Protein Subunits); 0 (Receptors, Glycine); 0 (Recombinant Proteins)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150421
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms7829



página 1 de 5 ir para página              
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde