5MKF

cryoEM Structure of Polycystin-2 in complex with calcium and lipids

5MKF の概要

• エントリーDOI: 10.2210/pdb5mkf/pdb
• EMDBエントリー: 3524
• 分子名称: Polycystin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: ca2+ signaling, cryoem, membrane protein structure, polycystin-2, trp channel, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 451223.77

構造登録者

Wilkes, M.,Madej, M.G.,Ziegler, C. (登録日: 2016-12-04, 公開日: 2017-01-18, 最終更新日: 2025-07-02)

主引用文献

Wilkes, M.,Madej, M.G.,Kreuter, L.,Rhinow, D.,Heinz, V.,De Sanctis, S.,Ruppel, S.,Richter, R.M.,Joos, F.,Grieben, M.,Pike, A.C.,Huiskonen, J.T.,Carpenter, E.P.,Kuhlbrandt, W.,Witzgall, R.,Ziegler, C.
Molecular insights into lipid-assisted Ca(2+) regulation of the TRP channel Polycystin-2.
Nat. Struct. Mol. Biol., 24:123-130, 2017

PubMed Abstract: 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.

PubMed: 28092368
DOI: 10.1038/nsmb.3357

実験手法

ELECTRON MICROSCOPY (4.2 Å)