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Retour aux sources: defining the structural basis of glutamate receptor activation

机译:来源:确定谷氨酸受体激活的结构基础

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Ionotropic glutamate receptors (iGluRs) are the major excitatory neurotransmitter receptor in the vertebrate CNS and, as a result, their activation properties lie at the heart of much of the neuronal network activity observed in the developing and adult brain. iGluRs have also been implicated in many nervous system disorders associated with postnatal development (e.g. autism, schizophrenia), cerebral insult (e.g. stroke, epilepsy), and disorders of the ageing brain (e.g. Alzheimer's disease, Parkinsonism). In view of this, an emphasis has been placed on understanding how iGluRs activate and desensitize in functional and structural terms. Early structural models of iGluRs suggested that the strength of the agonist response was primarily governed by the degree of closure induced in the ligand-binding domain (LBD). However, recent studies have suggested a more nuanced role for the LBD with current evidence identifying the iGluR LBD interface as a hotspot regulating agonist behaviour. Such ideas remain to be consolidated with recently solved structures of full-length iGluRs to account for the global changes that underlie channel activation and desensitization.
机译:离子型谷氨酸受体(iGluRs)是脊椎动物CNS中主要的兴奋性神经递质受体,因此,它们的激活特性是发育中和成年大脑中观察到的许多神经元网络活动的核心。 iGluR也涉及与产后发育相关的许多神经系统疾病(例如自闭症,精神分裂症),脑损伤(例如中风,癫痫)和大脑老化的疾病(例如阿尔茨海默氏病,帕金森病)。鉴于此,已经着重于理解iGluR如何在功能和结构方面激活和脱敏。 iGluR的早期结构模型表明,激动剂反应的强度主要受配体结合域(LBD)中诱导的闭合程度控制。然而,最近的研究表明,对于LBD而言,其作用更为细微,目前的证据表明iGluR LBD接口是调节激动剂行为的热点。此类思想仍需与最近解决的全长iGluR结构进行整合,以解决构成通道激活和脱敏作用的全局变化。

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