The Substrate Anion Selectivity Filter in the Human Erythrocyte <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif"><mml:msup><mml:mrow><mml:mi mathvariant="normal">C</mml:mi><mml:mi mathvariant="normal">l</mml:mi></mml:mrow><mml:mrow><mml:mo>−</mml:mo></mml:mrow></mml:msup><mml:mrow><mml:mrow><mml:mo>/</mml:mo></mml:mrow></mml:mrow><mml:mrow><mml:mi mathvariant="normal">H</mml:mi><mml:mi mathvariant="normal">C</mml:mi></mml:mrow><mml:msubsup><mml:mrow><mml:mi mathvariant="normal">O</mml:mi></mml:mrow><mml:mrow><mml:mn>3</mml:mn></mml:mrow><mml:mrow><mml:mo>−</mml:mo></mml:mrow></mml:msubsup></mml:math> Exchange Protein, AE1
Bibliographic record
Abstract
AE1 facilitates Cl-/HCO3- exchange across the erythrocyte membrane. To identify residues involved in substrate selection and translocation, we prepared an array of single cysteine mutants in an otherwise cysteineless background. These mutants spanning the C-terminal portion of the AE1 membrane domain from Phe806-Cys885 were characterized for functional activity when expressed in human embryonic kidney 293 cells by measurement of changes of intracellular pH associated with bicarbonate transport. To identify residues involved in substrate translocation, transport activity was assessed for each mutant before and after treatment with the following sulfhydryl reagents: anionic para-chloromercuibenzenesulfonate; permeant (2-aminoethyl)methanethiosulfonate; and cationic [2-(trimethylammonium)ethyl]methanethiosulfonate (MTSET). Among the 80 mutants, only certain key residues in the Val849-Leu863 region were inhibited by the sulfhydryl reagent, consistent with direct involvement of these sites in anion transport. In the last two transmembrane segments, only mutants in the extracellular portion of the transmembrane segments could be inhibited by sulfhydryl reagent, suggesting that the outer portions line the translocation channel and the inner portions have some other role. Sensitivity to cationic MTSET and effects of Cl- identified the substrate charge filter as Ser852-Leu857.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.006 |
| Meta-epidemiology (narrow) | 0.003 | 0.007 |
| Meta-epidemiology (broad) | 0.001 | 0.007 |
| Bibliometrics | 0.002 | 0.005 |
| Science and technology studies | 0.006 | 0.007 |
| Scholarly communication | 0.006 | 0.004 |
| Open science | 0.009 | 0.007 |
| Research integrity | 0.011 | 0.008 |
| Insufficient payload (model declined to judge) | 0.915 | 0.004 |
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; both teacher heads agree on what is shown here.
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".