Architecture of the TRPM subfamily Transient receptor potential melastatin (TRPM) ion channels constitute the largest TRP subfamily and are involved in many physiological processes. TRPM8 is the primary cold and menthol sensor, and TRPM4 is associated with cardiovascular disorders. Yin et al. and Autzen et al. shed light on the general architecture of the TRPM subfamily by solving the structures of TRPM8 and TRPM4, respectively (see the Perspective by Bae et al.). The three-layered architecture of the TRPM8 channel provides the framework for understanding the mechanisms of cold and menthol sensing. The two distinct closed states of TRPM4, with and without calcium, reveal a calcium-binding site and calcium-binding-induced conformational changes. Science, this issue p. 237, p. 228; see also p. 160 The structure of an ion channel provides a framework for understanding the mechanisms of cold and menthol sensing. Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo–electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer. The structure suggests that the menthol-binding site is located within the voltage-sensor–like domain and thus provides a structural glimpse of the design principle of the molecular transducer for cold and menthol sensation.

中文翻译：

---

冷和薄荷醇传感离子通道 TRPM8 的结构

TRPM 亚家族的结构瞬时受体电位褪黑素 (TRPM) 离子通道构成最大的 TRP 亚家族并参与许多生理过程。TRPM8 是主要的寒冷和薄荷醇传感器，TRPM4 与心血管疾病有关。殷等人。和 Autzen 等人。通过分别求解 TRPM8 和 TRPM4 的结构，阐明了 TRPM 亚家族的一般架构（参见 Bae 等人的观点）。TRPM8 通道的三层架构为理解冷感和薄荷醇感测机制提供了框架。TRPM4 的两种不同的闭合状态，有和没有钙，揭示了钙结合位点和钙结合诱导的构象变化。科学，这个问题 p。237 页。228; 另见第。160 离子通道的结构为理解冷感和薄荷醇感测机制提供了框架。瞬态受体电位褪黑素 (TRPM) 阳离子通道是参与多种生理过程的多模式传感器。在 TRPM 家族中，成员 8 (TRPM8) 是人类主要的寒冷和薄荷醇传感器。我们确定了全长 TRPM8 的低温电子显微镜结构，该结构来自有领捕蝇器，总分辨率约为 4.1 埃。我们的 TRPM8 结构揭示了一个三层架构。在已知的 TRP 结构中具有明显折叠的氨基末端结构域与羧基末端区域一起形成一个大的两层胞质环，与跨膜通道层广泛相互作用。