Structures of the extracellular regions of the group II/III metabotropic glutamate receptors
Structures of the extracellular regions of the group II/III metabotropic glutamate receptors
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DOI：
10.1073/pnas.0611577104
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发表时间：
2007-03-06
影响因子：
11.1
通讯作者：
Jingami, Hisato
中科院分区：
文献类型：
--
作者：
Muto, Takanori;Tsuchiya, Daisuke;Jingami, Hisato
代谢性谷氨酸受体在中枢神经系统兴奋性突触的激活中起重要作用。我们确定了整个II族受体的细胞外区域和III族受体的配体结合区域的晶体结构。组I、组II和组III之间的比较提供了可以解释组特异性激动剂歧视的结构基础。此外，II族的结构包括富含半胱氨酸的结构域，该结构域通过二硫桥与配体结合结构域紧密相连，这表明它可能在将配体诱导的构象变化传递到下游跨膜区域中发挥潜在作用。该结构还揭示了两个富含半胱氨酸的结构域之间的横向相互作用，这可能会刺激细胞表面二聚体受体的聚集。我们提出了二聚体受体与配体结合和蛋白质间重排结合的一般激活机制。
Metabotropic glutamate receptors play major roles in the activation of excitatory synapses in the central nerve system. We determined the crystal structure of the entire extracellular region of the group II receptor and that of the ligand-binding region of the group III receptor. A comparison among groups I, II, and III provides the structural basis that could account for the discrimination of group-specific agonists. Furthermore, the structure of group II includes the cysteine-rich domain, which is tightly linked to the ligand-binding domain by a disulfide bridge, suggesting a potential role in transmitting a ligand-induced conformational change into the downstream transmembrane region. The structure also reveals the lateral interaction between the two cysteine-rich domains, which could stimulate clustering of the dimeric receptors on the cell surface. We propose a general activation mechanism of the dimeric receptor coupled with both ligand-binding and interprotomer rearrangements.