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Structure paper

TitleMolecular insights into lipid-assisted Ca regulation of the TRP channel Polycystin-2.
Journal, issue, pagesNat Struct Mol Biol, Vol. 24, Issue 2, Page 123-130, Year 2017
Publish dateJan 16, 2017
AuthorsMartin 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 AbstractPolycystin-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.
External linksNat Struct Mol Biol / PubMed:28092368
MethodsEM (single particle)
Resolution4.2 - 4.3 Å
Structure data

3523

5mke

EMDB-3523, PDB-5mke:
cryoEM Structure of Polycystin-2 in complex with cations and lipids
Method: EM (single particle) / Resolution: 4.3 Å

3524

5mkf

EMDB-3524, PDB-5mkf:
cryoEM Structure of Polycystin-2 in complex with calcium and lipids
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CHS:
4-AMINO-5-CYCLOHEXYL-3-HYDROXY-PENTANOIC ACID

ChemComp-PX6:
1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE

ChemComp-PLM:
PALMITIC ACID

ChemComp-CA:
Unknown entry

Source
  • Homo sapiens (human)
KeywordsTRANSPORT PROTEIN / Ca2+ signaling / cryoEM / membrane protein structure / Polycystin-2 / TRP channel

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