Two domains of the smoothelin‐like 1 protein bind apo‐and calcium‐calmodulin independently
Bibliographic record
Abstract
The smoothelin‐like 1 protein (SMTNL1; also known as calponin homology (CH) domain‐associated smooth muscle, CHASM) is a modulator of vascular smooth muscle contractility and can bind to calmodulin (CaM) and tropomyosin. The intracellular calcium receptor CaM switches between calcium‐free (apo‐CaM) and calcium‐bound (Ca‐CaM) forms. Bioinformatic analysis of the SMTNL1 sequence predicted two CaM‐binding regions: CBD1, N‐terminal to the CH domain and CBD2, a previously described IQ motif within the CH domain. We sought to describe the contribution of SMTNL1's two CBDs to CaM binding in the presence or absence of calcium. Using a variety of assays (biochemical pull‐downs, surface plasmon resonance, NMR and intracellular co‐localization by microscopy), we determined that CBD1 binds preferentially to Ca‐CaM while CBD2 binds preferentially to apo‐CaM. Mutation of key acidic residues abolished apo‐CaM binding to CBD2, while hydrophobic residues in CBD1 were required for Ca‐CaM binding. The binding affinities (~4 ×10 −6 M) were similar for both. The association of SMTNL1 with apo‐CaM and Ca‐CaM suggest that endogenous SMTNL1 is always associated with CaM. This lead us to the conclusion that changes in the CaM binding to CBD1 or CBD2 may allow for downsteam effects, such as disruption of SMTNL1 binding to tropomyosin.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".