Department of Cardiology, Boston Children's Hospital, Boston, MA 02115.
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):E8201-E8210. doi: 10.1073/pnas.1810719115. Epub 2018 Aug 14.
The transient receptor potential ion channel subfamily M, member 7 (TRPM7), is a ubiquitously expressed protein that is required for mouse embryonic development. TRPM7 contains both an ion channel and an α-kinase. The channel domain comprises a nonselective cation channel with notable permeability to Mg and Zn Here, we report the closed state structures of the mouse TRPM7 channel domain in three different ionic conditions to overall resolutions of 3.3, 3.7, and 4.1 Å. The structures reveal key residues for an ion binding site in the selectivity filter, with proposed partially hydrated Mg ions occupying the center of the conduction pore. In high [Mg], a prominent external disulfide bond is found in the pore helix, which is essential for ion channel function. Our results provide a structural framework for understanding the TRPM1/3/6/7 subfamily and extend the knowledge base upon which to study the diversity and evolution of TRP channels.
瞬时受体电位离子通道亚家族 M，成员 7（TRPM7）是一种广泛表达的蛋白质，对于小鼠胚胎发育是必需的。TRPM7 既包含离子通道又包含 α-激酶。通道结构域包含一个非选择性阳离子通道，对 Mg 和 Zn 具有显著的通透性。在这里，我们报道了三种不同离子条件下的小鼠 TRPM7 通道结构域的关闭状态结构，整体分辨率分别为 3.3、3.7 和 4.1 Å。这些结构揭示了选择性过滤器中离子结合位点的关键残基，提出了部分水合的 Mg 离子占据传导孔的中心。在高 [Mg] 条件下，在孔螺旋中发现了一个明显的外部二硫键，这对于离子通道功能至关重要。我们的结果为理解 TRPM1/3/6/7 亚家族提供了一个结构框架，并扩展了研究 TRP 通道多样性和进化的知识库。
