Single Domain Metallothioneins: Supermetalation of Human MT 1a
Bibliographic record
Abstract
Metallothioneins are a family of small, cysteine rich proteins that have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as metallochaperones involved in the homeostasis of both essential zinc and copper. We report that human metallothionein 1a, well-known to coordinate 7 Zn(2+) or Cd(2+) ions with 20 cysteinyl thiols, will bind 8 structurally significant Cd(2+) ions, leading to the formation of the supermetalated Cd(8)-βα-rhMT 1a species, for which the structure is a novel single domain. ESI-mass spectrometry was used to determine the exact metalation status of the βα-rhMT. The derivative-shaped CD envelope of Cd(7)-βα-rhMT [peak extrema (+) 260 and (-) 239 nm] changed drastically upon formation of the Cd(8)-βα-rhMT with the appearance of a sharp monophasic CD band centered on 252 nm, a feature indicative of the loss of cluster symmetry. The structural significance of the eighth Cd(2+) ion was determined from a combination of direct and indirect (113)Cd nuclear magnetic resonance (NMR) spectra. In the case of Cd(8)-βα-rhMT, only four peaks were observed in the direct (113)Cd NMR spectrum. Significantly, while both of the isolated domains can be supermetalated forming Cd(4)-β-rhMT and Cd(5)-α-rhMT, Cd(8)-βα-rhMT and not Cd(9)-βα-rhMT was observed following addition of excess Cd(2+). We propose that both domains act in concert to coordinate the eighth Cd(2+) atom, and furthermore that this interaction results in a coalescence of the two domains leading to collapse of the two-domain structure. This is the first report of a possible single-"superdomain" metallothionein structure for Zn(2+) and Cd(2+) binding mammalian proteins. A computational model of a possible single-domain structure of Cd(8)-βα-rhMT is described.
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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 | 0.000 |
| 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".