Calexcitin B: a new calcium-sensor protein in the nervous system of the squid
Bibliographic record
Abstract
Calcium ions (Ca 2+) are paramount for cell viability and function. The Ca 2+ signalling pathways utilize specialized proteins, called Ca 2+ binding proteins (CaBPs). Calexcitin (CE) is a CaBP that putatively acts as an intracellular Ca 2+ -mediated messenger. CE is expressed specifically in the nervous system, and may play a critical role in memory. In this work, I elucidated the correct primary structure of CE and characterized its biochemical and biophysical properties. CE can bind three Ca 2+ at affinities similar to other Ca 2+ -sensor proteins. In addition, I have shown that CE is a member of the sarcoplasmic Ca 2+ binding protein (SCP) subfamily of the EF-hand superfamily. Like other SCPs, CE can bind Mg 2+ and has a complex Ca 2+ /Mg 2+ interplay that affects its structure. My studies have identified the physiological role of Mg 2+ binding and has shown that CE is a two domain protein that exists in three distinct conformational states: Apo-CE, has molten-globule characteristics; Mg 2+ -loaded CE possesses one native domain and the other domain is molten-globule like; Ca 2+ -loaded CE has both domains in native configuration. This indicates that under physiological concentrations of Mg 2+ and Ca 2+, Mg 2+ -CE represents the resting state of the molecule and Ca 2+ -CE is the active state. The backbone nuclei of CE has been assigned by nuclear magnetic resonance and the results show that CE is composed of nine a-helices, eight of which form the four EF-hands and the ninth is near the C-terminus. This result clarified previous discrepancies in the literature regarding the secondary structure of CE and lays the foundation for studying the protein dynamics of CE. Models of CE, based on related proteins, show that, in agreement with biophysical data, CE is composed of two domains that do not interact considerably. Furthermore, in agreement with biophysical data, the model shows a putative recessed hydrophobic pocket that may be involved in target recognition, analogous to other Ca 2+ -sensor proteins. This thesis provides the basis for future investigations into elucidating the precise physiological function of CE. In addition, it enhances our understanding on how CaBPs work and how we can exploit their function for practical neuroprotective applications.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".