鱼源ATP通道CALHM1开放态单颗粒冷冻电镜成像数据集

钙稳态调节剂 1 (CALHM1) 是一种电压门控 ATP 释放通道，在神经味觉信号传导和阿尔茨海默病的发病机制中起重要作用。在这里，我们展示了来自 Danio rerio 的全长 Ca-free CALHM1 的低温电子显微镜结构，总分辨率为 3.1 Å。我们的结构揭示了一种八聚体结构，孔径约为 20 Å，可能代表了活性构象。整体结构与同种型 CALHM2 的结构大不相同，CALHM2 形成非十聚体半通道和间隙连接。 N端小螺旋折叠回孔并与跨膜螺旋1形成反平行相互作用。结构分析表明，二聚体界面内的细胞外环1区域可能有助于寡聚体组装。确定了孔内的正电位带可以调节离子渗透。我们的结构提供了对 CALHM1 通道的组装和门控机制的见解。

Calcium homeostasis modulator 1 (CALHM1) is a voltage-gated ATP release channel that plays critical roles in neural gustatory signal transduction and the pathogenesis of Alzheimer’s disease. Here, we present the cryo-electron microscopy structure of full-length, Ca-free CALHM1 from Danio rerio, with an overall resolution of 3.1 Å. Our structure reveals an octameric assembly with a pore diameter of approximately 20 Å, which likely represents the active conformation. The overall structure differs greatly from that of isoform CALHM2, which forms non-decameric hemichannels and gap junctions. The N-terminal small helix folds back into the pore and forms an antiparallel interaction with transmembrane helix 1. Structural analysis indicates that the extracellular loop 1 region within the dimer interface may contribute to oligomeric assembly. We identified a positively charged electrostatic band within the pore that regulates ion permeation. Our structure provides insights into the assembly and gating mechanism of CALHM1 channels.

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背景概述

该数据集提供了鱼源ATP通道CALHM1开放态的单颗粒冷冻电镜成像数据，分辨率达3.1 Å，揭示了其八聚体结构和约20 Å的孔径，可能代表活性构象。这些结构信息有助于理解CALHM1在神经味觉信号和阿尔茨海默病中的功能机制，特别是通道的组装和门控过程。