Structures of the AMPA receptor incomplex with its auxiliary subunit cornichon
Structures of the AMPA receptor incomplex with its auxiliary subunit cornichon
复制标题
DOI：
10.1126/science.aay2783
复制
发表时间：
2019-12-06
期刊：
影响因子：
56.9
通讯作者：
Nakagawa, Terunaga
中科院分区：
文献类型：
--
作者：
Nakagawa, Terunaga
在大脑中，AMPA型谷氨酸受体（AMPAR）与其辅助亚基形成复合物，并介导大部分快速兴奋性神经传递。由这些复合物转导的信号对突触可塑性、学习和记忆至关重要。AMPAR辅助亚基的两个主要类别是跨膜AMPAR调节蛋白（TARP）和cornichon同系物（CNIH）;这些亚基几乎没有同源性，并在控制离子通道门控和AMPAR的运输中发挥不同的作用。在这里，我报告高分辨率的低温电子显微镜结构的AMPAR在复杂的CNIH 3。与其预测的膜拓扑结构相反，CNIH 3缺乏胞外结构域，而是含有四个跨膜螺旋。揭示了决定通道调节的蛋白质-蛋白质相互作用界面和复合物周围的脂质。这些结构为离子通道调节和AMPAR/CNIH 3复合物的组装提供了分子机制的见解。
In the brain, AMPA-type glutamate receptors (AMPARs) form complexes with their auxiliary subunits and mediate the majority of fast excitatory neurotransmission. Signals transduced by these complexes are critical for synaptic plasticity, learning, and memory. The two major categories of AMPAR auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs); these subunits share little homology and play distinct roles in controlling ion channel gating and trafficking of AMPAR. Here, I report high-resolution cryo-electron microscopy structures of AMPAR in complex with CNIH3. Contrary to its predicted membrane topology, CNIH3 lacks an extracellular domain and instead contains four membrane-spanning helices. The protein-protein interaction interface that dictates channel modulation and the lipids surrounding the complex are revealed. These structures provide insights into the molecular mechanism for ion channel modulation and assembly of AMPAR/CNIH3 complexes.