Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2 (PC2)
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".