Three-Dimensional Model for the Human Cl−/HCO3− Exchanger, AE1, by Homology to the E. coli ClC Protein
Bibliographic record
Abstract
AE1 mediates electroneutral 1:1 exchange of bicarbonate for chloride across the plasma membrane of erythrocytes and type A cells of the renal collecting duct. No high-resolution structure is available for the AE1 membrane domain, which alone is required for its transport activity. A recent electron microscopy structure of the AE1 membrane domain was proposed to have a similar protein fold to ClC chloride channels. We developed a three-dimensional homology model of the AE1 membrane domain, using the Escherichia coli ClC channel structure as a template. This model agrees well with a long list of biochemically established spatial constraints for AE1. To investigate the AE1 transport mechanism, we created point mutations in regions corresponding to E. coli ClC transport mechanism residues. When expressed in HEK293 cells, several mutants had Cl(-)/HCO3(-) exchange rates significantly different from that of wild-type AE1. When further assessed in Xenopus laevis oocytes, there were significant changes in the transport activity of several AE1 point mutants as assessed by changes in pH. None of the mutants, however, added an electrogenic component to AE1 transport activity. This indicates that the AE1 point mutants altered the transport activity of AE1, without changing its electrogenicity and stoichiometry. The homology model successfully identified residues in AE1 that are critical to AE1 transport activity. Thus, we conclude that AE1 has a similar protein fold to ClC chloride channels.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.003 |
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".