Positions of Polar Amino Acids Alter Interactions between Transmembrane Segments and Detergents
Bibliographic record
Abstract
α-Helical transmembrane (TM) segments in membrane proteins are comprised primarily of hydrophobic amino acids that accommodate insertion from water into the nonpolar membrane bilayer. In many such segments, however, polar residues are also present for structural or functional reasons. These latter residues impair the local favorable acyl interactions required for solvation by hydrophobic media such as phospholipids in native bilayers or detergents used for in vitro characterization. Using a series of Lys-tagged designed TM-like peptides (typified by KK-YAAAIAAIAWAIAAIAAAIAA-KKK) in which single-Asn residue substitutions (from Ile or Ala) were made successively from the center of the hydrophobic region toward the C-terminus, we demonstrate that polar residues strongly alter the nature of the interaction between TM segments and the solvating detergent. Through the application of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism spectroscopy, and tryptophan fluorescence, we observed drastic differences in the structures of the detergent-peptide complexes that contain relatively minor sequence differences. For example, the blue shift of the Trp fluorescence (indicating local detergent solvation at this location) differs by as much as ~10 nm depending upon the position of a single Asn substitution in an otherwise identical segment. The overall results suggest that polar point mutations occurring in a biological membrane will elicit comparable effects, placing a significant refolding burden on the local protein structure and potentially leading to disease states through altered protein--lipid interactions in membrane proteins.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".