Studies of the Molecular Basis for Cystic Fibrosis Using Purified Reconstituted CFTR Protein
Bibliographic record
Abstract
Studies of purified, reconstituted cystic fibrosis transmembrane conductance regulator (CFTR) protein have proven invaluable in defining those functions that are intrinsic to the CFTR molecule. Reconstitution of purified CFTR protein in planar lipid bilayers provided direct evidence that CFTR possesses intrinsic activity as a protein kinase A (PKA)-regulated chloride channel ( 1 ). Further, it appears that the regulation of the CFTR channel gate (the structure essential for opening and closing of the channel pore) reported in biological membranes has been recapitulated with fidelity in studies of reconstituted purified protein. For example, patch clamp studies on biological membranes revealed that ATP binding and/or hydrolysis by the PKA-phosphorylated CFTR channel caused channel opening and closing ( 2 - 6 ). This unique requirement for ATP in channel gating was also reported in reconstitution studies of the purified protein ( 7 , 8 ), indicating that the CFTR protein itself can mediate regulated chloride flux without the requirement for accessory proteins. These results also justify the use of purified protein in detailed biochemical and structural studies of mechanisms underlying the function of this protein. The CFTR molecule is known to be comprised of two membrane-spanning domains (TMDs), two nucleotide-binding domains (NBDs), and the phosphorylationdependent regulatory or R domain ( 9 ). However, to date, our understanding of the structure of these domains and the coordination of their activities is limited.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.001 | 0.001 |
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".