A Venus flytrap mechanism for activation and desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
A Venus flytrap mechanism for activation and desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
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DOI：
10.1074/jbc.271.26.15299
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发表时间：
1996-06-28
影响因子：
4.8
通讯作者：
Teichberg, VI
中科院分区：
文献类型：
--
作者：
Mano, I;Lamed, Y;Teichberg, VI
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)亚型谷氨酸受体通道的脱敏是影响突触兴奋时程的重要过程。脱敏后，受体通道关闭，激动剂亲和力增强。到目前为止，导致这些事件的结构重组的性质尚不清楚。基于AMPA受体的配体结合域和双叶细菌周质蛋白的结构同源性，我们现在证明激动剂与同种AMPA受体的GluR1亚单位的一个叶相互作用控制通道激活，而与另一个叶的额外相互作用导致通道脱敏。因此，我们认为AMPA受体通道向脱敏状态的转变涉及激动剂介导的其结合域的闭合叶构象的稳定，是一个类似于捕蝇器的过程。
Desensitization of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor channels is an important process shaping the time course of synaptic excitation. Upon desensitization, the receptor channel closes and the agonist affinity increases. So far, the nature of the structural rearrangements leading to these events was unknown. On the basis of the structural homology of the ligand binding domains of AMPA receptors and of the bilobated bacterial periplasmic proteins, we now show that agonist interaction with one lobe of the GluR1 subunit of homomeric AMPA receptors controls channel activation while additional interactions with the other lobe cause channel desensitization. Accordingly, we suggest that the transition of the AMPA receptor channel to the desensitized state involves the agonist-mediated stabilization of the closed lobe conformation of its binding domain and is a process akin to that used by the venus flytrap.