Crystal structure of a human GABAA receptor.

Abstract:

:Type-A γ-aminobutyric acid receptors (GABAARs) are the principal mediators of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signalling triggers hyperactive neurological disorders such as insomnia, anxiety and epilepsy. Here we present the first three-dimensional structure of a GABAAR, the human β3 homopentamer, at 3 Å resolution. This structure reveals architectural elements unique to eukaryotic Cys-loop receptors, explains the mechanistic consequences of multiple human disease mutations and shows an unexpected structural role for a conserved N-linked glycan. The receptor was crystallized bound to a previously unknown agonist, benzamidine, opening a new avenue for the rational design of GABAAR modulators. The channel region forms a closed gate at the base of the pore, representative of a desensitized state. These results offer new insights into the signalling mechanisms of pentameric ligand-gated ion channels and enhance current understanding of GABAergic neurotransmission.

journal_name

Nature

journal_title

Nature

authors

Miller PS,Aricescu AR

doi

10.1038/nature13293

subject

Has Abstract

pub_date

2014-08-21 00:00:00

pages

270-5

issue

7514

eissn

0028-0836

issn

1476-4687

pii

nature13293

journal_volume

512

pub_type

杂志文章

相关文献

NATURE文献大全
  • α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation.

    abstract::Parkinson's disease is the second most common neurodegenerative disorder. Growing evidence indicates a causative role of misfolded forms of the protein α-synuclein in the pathogenesis of Parkinson's disease. Intraneuronal aggregates of α-synuclein occur in Lewy bodies and Lewy neurites, the cytopathological hallmarks ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature10324

    authors: Bartels T,Choi JG,Selkoe DJ

    更新日期:2011-08-14 00:00:00

  • Recruitment of Drosophila Polycomb group proteins to chromatin by DSP1.

    abstract::Polycomb and trithorax group (PcG and trxG) proteins maintain silent and active transcriptional states, respectively, throughout development. In Drosophila, PcG and trxG proteins associate with DNA regions named Polycomb and trithorax response elements (PRE and TRE), but the mechanisms of recruitment are unknown. We p...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03386

    authors: Déjardin J,Rappailles A,Cuvier O,Grimaud C,Decoville M,Locker D,Cavalli G

    更新日期:2005-03-24 00:00:00

  • Antigen-induced B-cell death and elimination during germinal-centre immune responses.

    abstract::During an immune response, hypermutation of immunoglobulin genes in B cells proliferating within germinal centres (GCs) generates variant antibodies that react with higher affinity against either foreign or self antigens. Several experiments suggest that self-reactive B cells may be censored at this stage of the immun...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/375334a0

    authors: Shokat KM,Goodnow CC

    更新日期:1995-05-25 00:00:00

  • Structure of a presenilin family intramembrane aspartate protease.

    abstract::Presenilin and signal peptide peptidase (SPP) are intramembrane aspartyl proteases that regulate important biological functions in eukaryotes. Mechanistic understanding of presenilin and SPP has been hampered by lack of relevant structural information. Here we report the crystal structure of a presenilin/SPP homologue...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11801

    authors: Li X,Dang S,Yan C,Gong X,Wang J,Shi Y

    更新日期:2013-01-03 00:00:00

  • Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart.

    abstract::Acetylcholine (ACh) released on vagal stimulation reduces the heart rate by increasing K+ conductance of pacemaker cells in the sinoatrial (S-A) node. Fluctuation analysis of ACh-activated currents in pacemaker tissue showed this to be due to opening of a separate class of K+ channels gated by muscarinic ACh receptors...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/303250a0

    authors: Sakmann B,Noma A,Trautwein W

    更新日期:1983-05-19 00:00:00

  • Association between GTPase activators for Rho and Ras families.

    abstract::The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partia...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/359153a0

    authors: Settleman J,Albright CF,Foster LC,Weinberg RA

    更新日期:1992-09-10 00:00:00

  • Molecular cloning of Drosophila TFIID subunits.

    abstract::Transcription initiation factor TFIID is a multisubunit complex containing a TATA-box-binding factor (TFIID tau/TBP) and associated polypeptide factors (TAFs) with sizes ranging from M(r) approximately 20,000 to > 200,000. As a result of direct promoter interactions, TFIID nucleates the assembly of RNA polymerase II a...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/367484a0

    authors: Kokubo T,Gong DW,Wootton JC,Horikoshi M,Roeder RG,Nakatani Y

    更新日期:1994-02-03 00:00:00

  • Real-time spectroscopy of transition states in bacteriorhodopsin during retinal isomerization.

    abstract::Real-time investigations of the rearrangement of bonds during chemical transformations require femtosecond temporal resolution, so that the atomic vibrations within the reacting molecules can be observed. Following the development of lasers capable of emitting ultrashort laser flashes on this timescale, chemical react...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35107042

    authors: Kobayashi T,Saito T,Ohtani H

    更新日期:2001-11-29 00:00:00

  • Author Correction: Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

    abstract::In the Methods section of this Article, 'greater than' should have been 'less than' in the sentence 'Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distance that was at least 10 times greater than the whole-genome average for the individual sample. '. The Article ...

    journal_title:Nature

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41586-019-0883-2

    authors: Nik-Zainal S,Davies H,Staaf J,Ramakrishna M,Glodzik D,Zou X,Martincorena I,Alexandrov LB,Martin S,Wedge DC,Van Loo P,Ju YS,Smid M,Brinkman AB,Morganella S,Aure MR,Lingjærde OC,Langerød A,Ringnér M,Ahn SM,Boyault S

    更新日期:2019-02-01 00:00:00

  • White dwarf stars with carbon atmospheres.

    abstract::White dwarfs represent the endpoint of stellar evolution for stars with initial masses between approximately 0.07 and 8-10, where is the mass of the Sun (more massive stars end their life as either black holes or neutron stars). The theory of stellar evolution predicts that the majority of white dwarfs have a core mad...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature06318

    authors: Dufour P,Liebert J,Fontaine G,Behara N

    更新日期:2007-11-22 00:00:00

  • Identification of a protein encoded by the vpu gene of HIV-1.

    abstract::Human immunodeficiency virus 1 (HIV-1) is the aetiological agent of AIDS. The virus establishes lytic, latent and non-cytopathic productive infection in cells in culture. The complexity of virus-host cell interaction is reflected in the complex organization of the viral genome. In addition to the genes that encode the...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/334532a0

    authors: Cohen EA,Terwilliger EF,Sodroski JG,Haseltine WA

    更新日期:1988-08-11 00:00:00

  • Crystal structure of the specificity domain of ribonuclease P.

    abstract::RNase P is the only endonuclease responsible for processing the 5' end of transfer RNA by cleaving a precursor and leading to tRNA maturation. It contains an RNA component and a protein component and has been identified in all organisms. It was one of the first catalytic RNAs identified and the first that acts as a mu...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature01386

    authors: Krasilnikov AS,Yang X,Pan T,Mondragón A

    更新日期:2003-02-13 00:00:00

  • Allelic variation in a fatty-acyl reductase gene causes divergence in moth sex pheromones.

    abstract::Pheromone-based behaviours are crucial in animals from insects to mammals, and reproductive isolation is often based on pheromone differences. However, the genetic mechanisms by which pheromone signals change during the evolution of new species are largely unknown. In the sexual communication system of moths (Insecta:...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature09058

    authors: Lassance JM,Groot AT,Liénard MA,Antony B,Borgwardt C,Andersson F,Hedenström E,Heckel DG,Löfstedt C

    更新日期:2010-07-22 00:00:00

  • Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses.

    abstract::The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus)...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/328539a0

    authors: Franchini G,Gurgo C,Guo HG,Gallo RC,Collalti E,Fargnoli KA,Hall LF,Wong-Staal F,Reitz MS Jr

    更新日期:1987-08-06 00:00:00

  • Solvent-induced distortions and the curvature of alpha-helices.

    abstract::The alpha-helix defined in 1951 by Pauling et al. on the basis of model building and X-ray fibre diffraction data has 3.65 residues per turn (n) achieved with planar peptides, torsion angles of phi = -48 degrees and psi = -57 degrees and hydrogen bonds which are close to linear. Although X-ray analyses of proteins hav...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/306281a0

    authors: Blundell T,Barlow D,Borkakoti N,Thornton J

    更新日期:1983-11-17 00:00:00

  • Hypersensitive termination of the hypoxic response by a disordered protein switch.

    abstract::The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature21705

    authors: Berlow RB,Dyson HJ,Wright PE

    更新日期:2017-03-16 00:00:00

  • Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus.

    abstract::Myeloid precursors can be grown in vitro in the presence of specific growth factors; however, their expansion is limited by a competing process of terminal differentiation. Proto-oncogenes seem to be involved in cellular proliferation and/or differentiation and may also play a role in the myelopoietic process. Murine ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/318667a0

    authors: Blasi E,Mathieson BJ,Varesio L,Cleveland JL,Borchert PA,Rapp UR

    更新日期:1985-12-19 00:00:00

  • A simple structural feature is a major determinant of the identity of a transfer RNA.

    abstract::Analysis of a series of mutants of an Escherichia coli alanine transfer RNA shows that substitution of a single G-U base pair in the acceptor helix eliminates aminoacylation with alanine in vivo and in vitro. Introduction of that base pair into the analogous position of a cysteine and a phenylalanine transfer RNA conf...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/333140a0

    authors: Hou YM,Schimmel P

    更新日期:1988-05-12 00:00:00

  • Solid-like behaviour of unsheared sickle haemoglobin gels and the effects of shear.

    abstract::Pathogenesis in sickle cell disease depends on the polymerization of deoxyhaemoglobin S into long fibres followed by 'gel' formation. The 'gelation' renders the affected erythrocytes less deformable than normal so that they obstruct the microvasculature and the 'gelation' process has been one of the targets for the de...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/288622a0

    authors: Briehl RW

    更新日期:1980-12-11 00:00:00

  • Glutamate induces de novo growth of functional spines in developing cortex.

    abstract::Mature cortical pyramidal neurons receive excitatory inputs onto small protrusions emanating from their dendrites called spines. Spines undergo activity-dependent remodelling, stabilization and pruning during development, and similar structural changes can be triggered by learning and changes in sensory experiences. H...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature09986

    authors: Kwon HB,Sabatini BL

    更新日期:2011-06-02 00:00:00

  • Gravitationally redshifted absorption lines in the X-ray burst spectra of a neutron star.

    abstract::The fundamental properties of neutron stars provide a direct test of the equation of state of cold nuclear matter, a relationship between pressure and density that is determined by the physics of the strong interactions between the particles that constitute the star. The most straightforward method of determining thes...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature01159

    authors: Cottam J,Paerels F,Mendez M

    更新日期:2002-11-07 00:00:00

  • Molecular virology: was the 1918 flu avian in origin?

    abstract::Taubenberger et al. claim that the 1918 influenza virus was derived from an avian source and adapted to humans shortly before the pandemic. However, we do not believe that this conclusion, which has been widely disseminated in the popular press and in scientific journals, is supported by their phylogenetic evidence. ...

    journal_title:Nature

    pub_type: 评论,历史文章,杂志文章

    doi:10.1038/nature04824

    authors: Antonovics J,Hood ME,Baker CH

    更新日期:2006-04-27 00:00:00

  • Designing CD4 immunoadhesins for AIDS therapy.

    abstract::A newly-constructed antibody-like molecule containing the gp120-binding domain of the receptor for human immunodeficiency virus blocks HIV-1 infection of T cells and monocytes. Its long plasma half-life, other antibody-like properties, and potential to block all HIV isolates, make it a good candidate for therapeutic u...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/337525a0

    authors: Capon DJ,Chamow SM,Mordenti J,Marsters SA,Gregory T,Mitsuya H,Byrn RA,Lucas C,Wurm FM,Groopman JE

    更新日期:1989-02-09 00:00:00

  • Transporting and concentrating vibrational energy to promote isomerization.

    abstract::Visible-light absorption and transport of the resultant electronic excitations to a reaction centre through Förster resonance energy transfer1-3 (FRET) are critical to the operation of biological light-harvesting systems4, and are used in various artificial systems made of synthetic dyes5, polymers6 or nanodots7,8. Th...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-03081-y

    authors: Lau JA,Chen L,Choudhury A,Schwarzer D,Verma VB,Wodtke AM

    更新日期:2021-01-01 00:00:00

  • Structure of the UmuD' protein and its regulation in response to DNA damage.

    abstract::For life to be sustained, mistakes in DNA repair must be tolerated when damage obscures the genetic information. In bacteria such as Escherichia coli, DNA damage elicits the well regulated 'SOS response'. For the extreme case of damage that cannot be repaired by conventional enzymes, there are proteins that allow the ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/380727a0

    authors: Peat TS,Frank EG,McDonald JP,Levine AS,Woodgate R,Hendrickson WA

    更新日期:1996-04-25 00:00:00

  • Ploughing the deep sea floor.

    abstract::Bottom trawling is a non-selective commercial fishing technique whereby heavy nets and gear are pulled along the sea floor. The direct impact of this technique on fish populations and benthic communities has received much attention, but trawling can also modify the physical properties of seafloor sediments, water–sedi...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11410

    authors: Puig P,Canals M,Company JB,Martín J,Amblas D,Lastras G,Palanques A

    更新日期:2012-09-13 00:00:00

  • Characterization and inhibition of a cholecystokinin-inactivating serine peptidase.

    abstract::A cholecystokinin (CCK)-inactivating peptidase was purified and identified as a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10), a cytosolic subtilisin-like peptidase of previously unknown functions. The peptidase was found in neurons responding to cholecystokinin, as well as in non-neuronal cells. B...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/380403a0

    authors: Rose C,Vargas F,Facchinetti P,Bourgeat P,Bambal RB,Bishop PB,Chan SM,Moore AN,Ganellin CR,Schwartz JC

    更新日期:1996-04-04 00:00:00

  • A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans.

    abstract::How left/right functional asymmetry is layered on top of an anatomically symmetrical nervous system is poorly understood. In the nematode Caenorhabditis elegans, two morphologically bilateral taste receptor neurons, ASE left (ASEL) and ASE right (ASER), display a left/right asymmetrical expression pattern of putative ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02255

    authors: Johnston RJ,Hobert O

    更新日期:2003-12-18 00:00:00

  • Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins.

    abstract::The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive imm...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature15254

    authors: Bondy-Denomy J,Garcia B,Strum S,Du M,Rollins MF,Hidalgo-Reyes Y,Wiedenheft B,Maxwell KL,Davidson AR

    更新日期:2015-10-01 00:00:00

  • Publisher Correction: Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage.

    abstract::In this Article, owing to an error during the production process, in Fig. 1a, the dark blue and light blue wedges were incorrectly labelled as 'G•C → T•A' and 'G•C → A•T', instead of 'C•G → T•A' and 'C•G → A•T', respectively. Fig. 1 has been corrected online. ...

    journal_title:Nature

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41586-018-0070-x

    authors: Gaudelli NM,Komor AC,Rees HA,Packer MS,Badran AH,Bryson DI,Liu DR

    更新日期:2018-07-01 00:00:00