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Polycystin-2 (PC2) is a transient receptor potential (TRP) channel present in ciliary membranes of the kidney. PC2 shares a transmembrane fold with other TRP channels, in addition to an extracellular domain found in TRPP and TRPML channels. Using molecular dynamics (MD) simulations and cryoelectron microscopy we identify and characterize PIP2 and cholesterol interactions with PC2. PC2 is revealed to have a PIP binding site close to the equivalent vanilloid/lipid binding site in the TRPV1 channel. A 3.0-Å structure reveals a binding site for cholesterol on PC2. Cholesterol interactions with the channel at this site are characterized by MD simulations. The two classes of lipid binding sites are compared with sites observed in other TRPs and in Kv channels. These findings suggest PC2, in common with other ion channels, may be modulated by both PIPs and cholesterol, and position PC2 within an emerging model of the roles of lipids in the regulation and organization of ciliary membranes.

Original publication




Journal article


Structure (London, England : 1993)

Publication Date





169 - 184.e5


Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.


Animals, Humans, Cholesterol, Phosphatidylinositol Phosphates, Cryoelectron Microscopy, Binding Sites, Protein Structure, Secondary, Protein Binding, Models, Molecular, TRPP Cation Channels, Molecular Dynamics Simulation, Sf9 Cells