β亚基的非典型M2片段赋予抑制性甘氨酸受体通道对印防己毒素的抗性。
The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels.
作者信息
Pribilla I, Takagi T, Langosch D, Bormann J, Betz H
机构信息
Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
出版信息
EMBO J. 1992 Dec;11(12):4305-11. doi: 10.1002/j.1460-2075.1992.tb05529.x.
Abstract
Purified preparations of the inhibitory glycine receptor (GlyR) contain alpha and beta subunits, which share homologous primary structures and a common transmembrane topology with other members of the ligand-gated ion channel superfamily. Here, a beta subunit-specific antiserum was shown to precipitate the [3H]strychnine binding sites localized on alpha subunits from membrane extracts of both rat spinal cord and mammalian cells co-transfected with alpha and beta cDNAs. Further, inhibition of alpha homo-oligomeric GlyRs by picrotoxinin, a non-competitive blocker of ion flow, was reduced 50- to 200-fold for alpha/beta hetero-oligomeric receptors generated by cotransfection. Site-directed mutagenesis identified residues within the second predicted transmembrane segment (M2) of the beta subunit as major determinants of picrotoxinin resistance. These data implicate the M2 segment in blocker binding to and lining of the GlyR chloride channel.
摘要
纯化的抑制性甘氨酸受体（GlyR）制剂包含α和β亚基，它们与配体门控离子通道超家族的其他成员具有同源的一级结构和共同的跨膜拓扑结构。在此，一种β亚基特异性抗血清被证明能从大鼠脊髓和共转染了α和β cDNA的哺乳动物细胞的膜提取物中沉淀出位于α亚基上的[3H]士的宁结合位点。此外，对于通过共转染产生的α/β异源寡聚体受体，离子流的非竞争性阻断剂印防己毒素对α同源寡聚体GlyRs的抑制作用降低了50至200倍。定点诱变确定β亚基第二个预测跨膜片段（M2）内的残基是印防己毒素抗性的主要决定因素。这些数据表明M2片段参与了阻断剂与GlyR氯离子通道的结合及通道内衬。
相似文献
1
The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels.β亚基的非典型M2片段赋予抑制性甘氨酸受体通道对印防己毒素的抗性。
EMBO J. 1992 Dec;11(12):4305-11. doi: 10.1002/j.1460-2075.1992.tb05529.x.
2
Functional properties of strychnine-sensitive glycine receptors expressed in Xenopus oocytes injected with a single mRNA.注射单一信使核糖核酸（mRNA）的非洲爪蟾卵母细胞中表达的士的宁敏感性甘氨酸受体的功能特性
Neurosci Res. 1991 Jun;11(1):28-40. doi: 10.1016/0168-0102(91)90064-6.
3
The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes.人类甘氨酸受体β亚基：人类和小鼠基因的一级结构、功能特性及染色体定位
Brain Res Mol Brain Res. 1996 Jan;35(1-2):211-9.
4
Mechanism for the channel-opening reaction of strychnine-sensitive glycine receptors on cultured embryonic mouse spinal cord cells.士的宁敏感型甘氨酸受体在培养的胚胎小鼠脊髓细胞上的通道开放反应机制。
Biochemistry. 1994 Jun 21;33(24):7718-30. doi: 10.1021/bi00190a027.
5
Functional chloride channels by mammalian cell expression of rat glycine receptor subunit.
Neuron. 1989 May;2(5):1491-7. doi: 10.1016/0896-6273(89)90195-5.
6
Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site.配体门控离子通道受体的拮抗作用：甘氨酸受体α亚基的两个结构域形成士的宁结合位点。
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1765-9. doi: 10.1073/pnas.89.5.1765.
7
Synthetic peptides and four-helix bundle proteins as model systems for the pore-forming structure of channel proteins. II. Transmembrane segment M2 of the brain glycine receptor is a plausible candidate for the pore-lining structure.合成肽和四螺旋束蛋白作为通道蛋白成孔结构的模型系统。II. 脑甘氨酸受体的跨膜片段M2是孔衬结构的一个合理候选者。
J Biol Chem. 1993 Jul 15;268(20):14608-15.
8
Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation.新生和成年甘氨酸受体α亚基的激动剂药理学：鉴定参与牛磺酸激活的氨基酸残基。
EMBO J. 1992 Jun;11(6):2025-32. doi: 10.1002/j.1460-2075.1992.tb05259.x.
9
Functional expression in Xenopus oocytes of the strychnine binding 48 kd subunit of the glycine receptor.士的宁结合的甘氨酸受体48kd亚基在非洲爪蟾卵母细胞中的功能表达。
EMBO J. 1989 Mar;8(3):695-700. doi: 10.1002/j.1460-2075.1989.tb03428.x.
10
Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers.跨膜片段M2内的残基决定了甘氨酸受体同型和异型寡聚体的氯离子传导性。
EMBO J. 1993 Oct;12(10):3729-37. doi: 10.1002/j.1460-2075.1993.tb06050.x.
引用本文的文献
1
Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.里程碑式回顾：揭开甘氨酸受体复合物的蛋白质组学奥秘
J Neurochem. 2025 Apr;169(4):e70061. doi: 10.1111/jnc.70061.
2
An anatomical and physiological basis for flexible coincidence detection in the auditory system.听觉系统中灵活的同时性检测的解剖学和生理学基础。
Elife. 2025 Apr 15;13:RP100492. doi: 10.7554/eLife.100492.
3
Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.一种三环磺胺对甘氨酸受体的变构调节和直接激活作用
Sci Rep. 2025 Feb 14;15(1):5515. doi: 10.1038/s41598-025-90209-7.
4
Downregulation of Ribosomal Protein Genes Is Revealed in a Model of Rat Hippocampal Neuronal Culture Activation with GABA(A)R/GlyRa2 Antagonist Picrotoxin.GABA(A)R/GlyRa2 拮抗剂 picrotoxin 激活大鼠海马神经元培养物模型中核糖体蛋白基因下调。
Cells. 2024 Feb 23;13(5):383. doi: 10.3390/cells13050383.
5
An Anatomical and Physiological Basis for Flexible Coincidence Detection in the Auditory System.听觉系统中灵活符合检测的解剖学和生理学基础。
bioRxiv. 2024 Nov 21:2024.02.29.582808. doi: 10.1101/2024.02.29.582808.
6
Glycine Receptor β-Targeting Autoantibodies Contribute to the Pathology of Autoimmune Diseases.靶向甘氨酸受体β的自身抗体促成自身免疫性疾病的病理过程。
Neurol Neuroimmunol Neuroinflamm. 2024 Mar;11(2):e200187. doi: 10.1212/NXI.0000000000200187. Epub 2024 Jan 12.
7
Role of the Glycine Receptor β Subunit in Synaptic Localization and Pathogenicity in Severe Startle Disease.甘氨酸受体β亚单位在严重惊吓病中的突触定位和致病性中的作用。
J Neurosci. 2024 Jan 10;44(2):e0837232023. doi: 10.1523/JNEUROSCI.0837-23.2023.
8
Asymmetric gating of a human hetero-pentameric glycine receptor.人类异源五聚体甘氨酸受体的非对称门控。
Nat Commun. 2023 Oct 11;14(1):6377. doi: 10.1038/s41467-023-42051-6.
9
Glycine encephalopathy.甘氨酸脑病
Egypt J Neurol Psychiatr Neurosurg. 2022;58(1):132. doi: 10.1186/s41983-022-00567-6. Epub 2022 Nov 17.
10
Structure and Mechanism of Glycine Receptor Elucidated by Cryo-Electron Microscopy.冷冻电子显微镜解析甘氨酸受体的结构与机制
Front Pharmacol. 2022 Aug 9;13:925116. doi: 10.3389/fphar.2022.925116. eCollection 2022.
本文引用的文献
1
The arrangement of the subunits of the acetylcholine receptor of Torpedo californica.加州电鳐乙酰胆碱受体亚基的排列
J Biol Chem. 1983 Jun 10;258(11):6678-81.
2
Convulsant-induced depression of amino acid responses in cultured mouse spinal neurones studied under voltage clamp.在电压钳制条件下对培养的小鼠脊髓神经元中惊厥剂诱导的氨基酸反应抑制作用的研究。
Br J Pharmacol. 1983 Dec;80(4):619-29. doi: 10.1111/j.1476-5381.1983.tb10051.x.
3
Photoaffinity-labelling of the glycine receptor of rat spinal cord.大鼠脊髓甘氨酸受体的光亲和标记
Eur J Biochem. 1983 Apr 5;131(3):519-25. doi: 10.1111/j.1432-1033.1983.tb07292.x.
4
Purification by affinity chromatography of the glycine receptor of rat spinal cord.大鼠脊髓甘氨酸受体的亲和层析纯化
J Biol Chem. 1982 Aug 25;257(16):9389-93.
5
UV light-induced cross-linking of strychnine to the glycine receptor of rat spinal cord membranes.紫外线诱导士的宁与大鼠脊髓膜甘氨酸受体的交联。
Biochem Biophys Res Commun. 1981 Oct 30;102(4):1330-5. doi: 10.1016/s0006-291x(81)80157-x.
6
Solubilization of the glycine receptor from rat spinal cord.大鼠脊髓甘氨酸受体的增溶作用。
Brain Res. 1981 Dec 7;226(1-2):273-9. doi: 10.1016/0006-8993(81)91099-4.
7
GABA-benzodiazepine-barbiturate receptor interactions.γ-氨基丁酸-苯二氮䓬-巴比妥酸盐受体相互作用
J Neurochem. 1981 Jul;37(1):1-13. doi: 10.1111/j.1471-4159.1981.tb05284.x.
8
Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence.从cDNA序列推导的加州电鳐乙酰胆碱受体α亚基前体的一级结构
Nature. 1982 Oct 28;299(5886):793-7. doi: 10.1038/299793a0.
9
Modulation by picrotoxin and IPTBO of 3H-flunitrazepam binding to the GABA/benzodiazepine receptor complex of rat cerebellum.印防己毒素和IPTBO对3H-氟硝西泮与大鼠小脑GABA/苯二氮䓬受体复合物结合的调节作用。
Life Sci. 1981 Jan 19;28(3):307-13. doi: 10.1016/0024-3205(81)90738-4.
10
Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord.单克隆抗体和肽图谱分析揭示了大鼠脊髓甘氨酸受体亚基之间的结构相似性。
Proc Natl Acad Sci U S A. 1984 Nov;81(22):7224-7. doi: 10.1073/pnas.81.22.7224.
Zotero 插件