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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structures of the extracellular regions of the group Ⅱ/Ⅲ metabotropic glutamate receptors
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Structures of the extracellular regions of the group Ⅱ/Ⅲ metabotropic glutamate receptors

机译：Ⅱ/Ⅲ型代谢型谷氨酸受体细胞外区域的结构

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摘要

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.
机译：代谢型谷氨酸受体在中枢神经系统兴奋性突触的激活中起主要作用。我们确定了Ⅱ族受体的整个胞外区和Ⅲ族受体的配体结合区的晶体结构。 Ⅰ，Ⅱ和Ⅲ组之间的比较提供了可解释区分组特异性激动剂的结构基础。此外，Ⅱ族的结构包括富含半胱氨酸的结构域，该结构域通过二硫键与配体结合结构域紧密相连，表明在将配体诱导的构象变化传递到下游跨膜区域中具有潜在作用。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上的二聚体受体聚集。我们提出了二聚体受体配体结合和proprotomer重排耦合的一般激活机制。

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