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-Structure paper
タイトル | Molecular insights into lipid-assisted Ca regulation of the TRP channel Polycystin-2. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 24, Issue 2, Page 123-130, Year 2017 |
掲載日 | 2017年1月16日 |
著者 | Martin Wilkes / M Gregor Madej / Lydia Kreuter / Daniel Rhinow / Veronika Heinz / Silvia De Sanctis / Sabine Ruppel / Rebecca M Richter / Friederike Joos / Marina Grieben / Ashley C W Pike / Juha T Huiskonen / Elisabeth P Carpenter / Werner Kühlbrandt / Ralph Witzgall / Christine Ziegler / |
PubMed 要旨 | Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca signaling pathways. Malfunctioning Ca regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here ...Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca signaling pathways. Malfunctioning Ca regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter and in the large exoplasmic domain (TOP domain), which displays differing N-glycosylation. The more open structure has one cation bound below the selectivity filter (single-ion mode, PC2), whereas multiple cations are bound along the translocation pathway in the second structure (multi-ion mode, PC2). Ca binding at the entrance of the selectivity filter suggests Ca blockage in PC2, and we observed density for the Ca-sensing C-terminal EF hand in the unblocked PC2 state. The states show altered interactions of lipids with the pore loop and TOP domain, thus reflecting the functional diversity of PC2 at different locations, owing to different membrane compositions. |
リンク | Nat Struct Mol Biol / PubMed:28092368 |
手法 | EM (単粒子) |
解像度 | 4.2 - 4.3 Å |
構造データ | |
化合物 | ChemComp-NAG: ChemComp-CHS: ChemComp-PX6: ChemComp-PLM: ChemComp-CA: |
由来 |
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キーワード | TRANSPORT PROTEIN (運搬体タンパク質) / Ca2+ signaling / cryoEM (低温電子顕微鏡法) / membrane protein structure (生体膜) / Polycystin-2 / TRP channel (TRPチャネル) |