Format

Send to

Choose Destination
Nat Commun. 2018 Mar 22;9(1):1192. doi: 10.1038/s41467-018-03606-0.

Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.

Su Q1,2,3, Hu F1,3,4, Liu Y4,5,6,7, Ge X1,2, Mei C8, Yu S8, Shen A8, Zhou Q1,3,4,9, Yan C1,2,3,9, Lei J1,2,3, Zhang Y10,11,12,13, Liu X14,15,16,17,18, Wang T19,20,21,22.

Author information

1
Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing, 100084, China.
2
School of Life Sciences, Tsinghua University, Beijing, 100084, China.
3
Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China.
4
School of Medicine, Tsinghua University, Beijing, 100084, China.
5
X-Lab for Transmembrane Signaling Research, Department of Biomedical Engineering and McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
6
School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
7
Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China, 102402.
8
Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China.
9
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
10
Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing, 100084, China. zhangyanqing15@mail.tsinghua.edu.cn.
11
School of Life Sciences, Tsinghua University, Beijing, 100084, China. zhangyanqing15@mail.tsinghua.edu.cn.
12
Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China. zhangyanqing15@mail.tsinghua.edu.cn.
13
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China. zhangyanqing15@mail.tsinghua.edu.cn.
14
School of Life Sciences, Tsinghua University, Beijing, 100084, China. liu-lab@vip.163.com.
15
School of Medicine, Tsinghua University, Beijing, 100084, China. liu-lab@vip.163.com.
16
X-Lab for Transmembrane Signaling Research, Department of Biomedical Engineering and McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China. liu-lab@vip.163.com.
17
School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China. liu-lab@vip.163.com.
18
Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China, 102402. liu-lab@vip.163.com.
19
Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing, 100084, China. wangtingliang@mail.tsinghua.edu.cn.
20
Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China. wangtingliang@mail.tsinghua.edu.cn.
21
School of Medicine, Tsinghua University, Beijing, 100084, China. wangtingliang@mail.tsinghua.edu.cn.
22
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China. wangtingliang@mail.tsinghua.edu.cn.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center