Calcium homeostasis modulators (CALHMs/CLHMs) comprise a family of pore‐forming protein complexes assembling into voltage‐gated, Ca²⁺‐sensitive, nonselective channels. These complexes contain an ion‐conduction pore sufficiently wide to permit the passing of ATP molecules serving as neurotransmitters. While their function and structure information is accumulating, the precise mechanisms of these channel complexes remain to be full understood. Here, we present the structure of the Caenorhabditis elegans CLHM1 channel in its open state solved through single‐particle cryo‐electron microscopy at 3.7‐Å resolution. The transmembrane region of the channel structure of the dominant class shows an assembly of 10‐fold rotational symmetry in one layer, and its cytoplasmic region is involved in additional twofold symmetrical packing in a tail‐to‐tail manner. Furthermore, we identified a series of amino acid residues critical for the regulation of Ce CLHM1 channel using functional assays, electrophysiological analyses as well as structural‐based analysis. Our structure and function analyses provide new insights into the mechanisms of CALHM channels.

中文翻译：

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秀丽隐杆线虫 CLHM1 离子通道的冷冻电镜结构。


钙稳态调节剂 (CALHMs/CLHMs) 包含一系列成孔蛋白复合物，组装成电压门控、Ca ²⁺敏感、非选择性通道。这些复合物含有足够宽的离子传导孔，允许作为神经递质的 ATP 分子通过。虽然它们的功能和结构信息不断积累，但这些通道复合体的精确机制仍有待充分了解。在这里，我们展示了通过单粒子冷冻电子显微镜以 3.7-Å 分辨率解析的处于开放状态的秀丽隐杆线虫CLHM1 通道的结构。优势类通道结构的跨膜区显示出一层10重旋转对称的组装，其细胞质区以尾对尾的方式参与额外的双重对称堆积。此外，我们通过功能测定、电生理分析以及基于结构的分析，鉴定了一系列对Ce CLHM1 通道调节至关重要的氨基酸残基。我们的结构和功能分析为 CALHM 通道的机制提供了新的见解。