OSCA/TMEM63 is a newly identified family of mechanically activated (MA) ion channels in plants and animals, respectively, which convert physical forces into electrical signals or trigger intracellular cascades and are essential for eukaryotic physiology. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. However, the molecular architecture of the mammalian TMEM63 proteins remains unclear. Here we elucidate the structure of human TMEM63A in the presence of calcium by single particle cryo-EM, revealing a distinct monomeric architecture containing eleven transmembrane helices. It has structural similarity to the single subunit of the Arabidopsis thaliana OSCA proteins. We locate the ion permeation pathway within the monomeric configuration and observe a nonprotein density resembling lipid. These results lay a foundation for understanding the structural organization of OSCA/TMEM63A family proteins.

中文翻译：

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人TMEM63A蛋白的单体结构

OSCA/TMEM63 是植物和动物中新发现的机械激活 (MA) 离子通道家族，它们将物理力转化为电信号或触发细胞内级联，对于真核生理学至关重要。OSCA 和相关的 TMEM16 以及跨膜通道样 (TMC) 蛋白形成具有两个孔的同二聚体。然而，哺乳动物 TMEM63 蛋白的分子结构仍不清楚。在这里，我们通过单粒子冷冻电镜阐明了钙存在下人 TMEM63A 的结构，揭示了包含 11 个跨膜螺旋的独特单体结构。它与拟南芥OSCA 蛋白的单个亚基具有结构相似性。我们将离子渗透途径定位在单体构型内，并观察到类似于脂质的非蛋白质密度。这些结果为理解 OSCA/TMEM63A 家族蛋白的结构组织奠定了基础。