Structure of the mammalian TRPM7, a magnesium channel required during embryonic development.
Structure of the mammalian TRPM7, a magnesium channel required during embryonic development.
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哺乳动物 TRPM7 的结构，胚胎发育过程中所需的镁通道
DOI：
10.1073/pnas.1810719115
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发表时间：
2018-08-28
影响因子：
11.1
通讯作者：
Clapham DE
中科院分区：
文献类型：
--
作者：
Duan J;Li Z;Li J;Hulse RE;Santa-Cruz A;Valinsky WC;Abiria SA;Krapivinsky G;Zhang J;Clapham DE
离子通道是跨越生物膜的成孔蛋白。瞬时受体电位离子通道是离子通道蛋白的一个亚类，具有对钠、钙、镁、锌等阳离子的非选择性通透性和低电压敏感性，其门控仍然是一个活跃的研究领域。TRPM6和TRPM7广泛表达，在早期胚胎发育中发挥重要作用。独一无二的是，这些通道还包括一个活性激酶结构域。TRPM6和TRPM7的功能与蛋白水解性切割蛋白激酶结构域有关，然后将其转移到细胞核，使组蛋白磷酸化，调节基因表达。在这里，我们描述了TRPM7跨膜区的结构，并将其特征与其他离子通道进行了比较。瞬时受体电位离子通道亚家族M，成员7(TRPM7)是一种普遍表达的蛋白质，是小鼠胚胎发育所必需的。TRPM7既含有离子通道，又含有α-激酶。通道结构域包括对镁、锌离子具有显著渗透性的非选择性阳离子通道。在这里，我们报告了小鼠TRPM7通道结构域在三种不同离子条件下的闭态结构，总分辨率分别为3.3，3.7和4.1？结构揭示了选择性过滤器中离子结合位置的关键残基，建议的部分水合的镁离子占据了导电孔的中心。在高[Mg~(2+)]时，在孔道螺旋中发现了一个重要的外部二硫键，这是离子通道功能所必需的。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。
Ion channels are pore-forming proteins spanning biological membranes. Transient receptor potential ion channels are a subclass of ion channel proteins, characterized by nonselective permeability to cations such as sodium, calcium, magnesium, and zinc, and little voltage sensitivity; their gating is still an area of active investigation. TRPM6 and TRPM7 are ubiquitously expressed with prominent roles in early embryonic development. Uniquely, these channels also include an active kinase domain. The functions of TRPM6 and TRPM7 are correlated with proteolytic cleavage of the kinase domain, which is then translocated to the nucleus to phosphorylate histones and regulate gene expression. Here we describe the structure of the TRPM7 transmembrane regions and compare its features to other ion channels. 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 Mg2+ and Zn2+. 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 Mg2+ ions occupying the center of the conduction pore. In high [Mg2+], 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.
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影响因子：
7.7
作者：
Fan C;Choi W;Sun W;Du J;Lü W
通讯作者：
Lü W
DOI：
10.1387/ijdb.150196lr
发表时间：
2015
期刊：
The International journal of developmental biology
影响因子：
--
作者：
Komiya Y;Runnels LW
通讯作者：
Runnels LW
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Chen Q;She J;Zeng W;Guo J;Xu H;Bai XC;Jiang Y
通讯作者：
Jiang Y