Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing, 100084, China.
School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Nat Commun. 2018 Mar 22;9(1):1192. doi: 10.1038/s41467-018-03606-0.
PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π-π interactions, suggesting a potential PKD2L1 gating mechanism.
PKD2L1，也称为 TRPP 亚家族（多囊 TRP 通道）中的 TRPP3，参与酸味感觉和其他依赖 pH 值的过程。PKD2L1 被认为是一种非选择性阳离子通道，可受电压、质子和钙调节。尽管它非常重要，但 PKD2L1 调节的分子机制在很大程度上尚不清楚。在这里，我们通过冷冻电镜确定了 PKD2L1 的原子结构，分辨率为 3.38Å，几乎所有残基的侧链都被分配。与它的同源物 PKD2 不同，PKD2L1 的孔螺旋（PH）和跨膜片段 6（S6），参与上和下门的打开，采用开放构象。PKD2L1 与基于 PKD2 的同源模型的结构比较表明，孔域扩张通过一系列 π-π 相互作用与电压感应域（VSD）的构象变化偶联，提示了一种潜在的 PKD2L1 门控机制。
