美国范德比尔特大学医学院Terunaga Nakagawa报道了AMPA受体与其辅助亚基cornichon形成的复合物结构。2019年12月6日出版的《科学》发表了这项成果。

研究人员报道了AMPA型谷氨酸受体（AMPAR）与cornichon同源物（CNIH）复合的高分辨率冷冻电子显微镜结构。与预期的膜拓扑结构相反，CNIH3缺少细胞外域，而是包含四个跨膜的螺旋。这揭示了决定通道调节的蛋白-蛋白相互作用界面和复合物周围的脂质。这些结构提供了离子通道调节和AMPAR/CNIH3复合物组装分子机制的见解。

据介绍，在大脑中，AMPAR与它们的辅助亚基形成复合物，并介导大多数快速兴奋性神经传递。这些复合物转导的信号对于突触可塑性、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CNIH。这些亚基几乎没有同源性，并且在控制AMPAR的离子通道门控和运输中起不同的作用。

附：英文原文

Title: Structures of the AMPA receptor in complex with its auxiliary subunit cornichon

Author: Terunaga Nakagawa

Issue&Volume: 2019/12/06

Abstract: 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.

DOI: 10.1126/science.aay2783

Source: https://science.sciencemag.org/content/366/6470/1259