RT Journal Article
SR Electronic
T1 Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2 (PC2)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 589515
DO 10.1101/589515
A1 Qinrui Wang
A1 George Hedger
A1 Prafulla Aryal
A1 Mariana Grieben
A1 Chady Nasrallah
A1 Agnese Baronina
A1 Ashley C.W. Pike
A1 Jiye Shi
A1 Elisabeth P. Carpenter
A1 Mark S.P. Sansom
YR 2019
UL http://biorxiv.org/content/early/2019/03/26/589515.abstract
AB Polycystin-2 (PC2) is a member of the TRPP subfamily of TRP channels and is present in ciliary membranes of the kidney. PC2 can be either homo-tetrameric, or heterotetrameric with PC1. PC2 shares a common transmembrane fold with other TRP channels, in addition to having a novel extracellular domain. Several TRP channels have been suggested to be regulated by lipids, including phosphatidylinositol phosphates (PIPs). We have combined molecular dynamics simulations with cryoelectron microscopy to explore possible lipid interactions sites on PC2. We propose that PC2 has a PIP-binding site close to the equivalent vanilloid/lipid-binding site in the TRPV1 channel. A 3.0 Å cryoelectron microscopy map reveals a binding site for cholesterol on PC2. Cholesterol interactions with the channel at this site are further characterized by MD simulations. These results help to position PC2 within an emerging model of the complex roles of lipids in the regulation and organization of ciliary membranes.