Martinez-Sanchez Antonio, Laugks Ulrike, Kochovski Zdravko, Papantoniou Christos, Zinzula Luca, Baumeister Wolfgang, Lučić Vladan
Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Department of Computer Sciences, Faculty of Sciences, University of Oviedo, Federico Garcia Lorca 18, 33007, Spain.
Sci Adv. 2021 Mar 5;7(10). doi: 10.1126/sciadv.abe6204. Print 2021 Mar.
Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre- and postsynaptic proteins. Here, we used cryo-electron tomography to visualize synaptic complexes together with their native environment comprising interacting proteins and lipids on a 2- to 4-nm scale. Using template-free detection and classification, we showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in plasma membrane. These data support the hypothesis that synaptic function is carried by precisely organized trans-synaptic units. It provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their function.
突触传递的特点是快速、紧密耦合的过程以及复杂的信号通路，这需要精确的蛋白质组织，例如先前报道的突触前和突触后蛋白质的纳米域共定位。在这里，我们使用冷冻电子断层扫描在2到4纳米的尺度上可视化突触复合体及其包含相互作用的蛋白质和脂质的天然环境。通过无模板检测和分类，我们表明三方跨突触组装体（子柱）将突触小泡与突触后受体相连，并确定直接相互作用的复合体之间的特定位移是子柱的特征。此外，我们获得了嵌入质膜的离子型谷氨酸受体生理组成的从头平均结构。这些数据支持突触功能由精确组织的跨突触单元承载的假设。它为进一步探索连接不同细胞或细胞区域且可能需要弱相互作用或瞬时相互作用来发挥其功能的突触和其他大分子组装体提供了一个框架。
