Overexpression, purification of GSK3β and its interaction with an inhibitory fragment of the psychiatric risk protein DISC1
Bibliographic record
Abstract
Disrupted in Schizophrenia 1(DISC1) is a candidate risk gene in a number of major mental illnesses, e.g. depression, bipolar disorder and schizophrenia. DISC1 is a scaffold protein that interacts with a myriad of proteins, forming a large protein-protein-interaction network that coordinates various stages of brain development. Our lab is interested to understand how the structure of DISC1 facilitates its function in brain development. One of DISC1's interactors is the enzyme glycogen synthase kinase 3 (GSK-3). As a target for lithium, GSK3 is itself implicated in bipolar disorder. Through physical interactions, DISC1 inhibits GSK3 's function in the canonical Wnt/-catenin signalling pathway, which controls the proliferation of neural progenitors. The full length DISC1 protein is composed of 854 amino acids. The most potent GSK3 inhibitory region has been mapped to a short region in the N-terminus (residue 195-238). This 44 amino acid region (DISC1-44mer) can inhibit and bind GSK3 in in vitro experiments. To understand the mechanism of how DISC1 inhibits GSK3 , we are pursuing structural studies of GSK3 in complex with different truncations of DISC1. We will present our progress towards the structural studies of this important complex that is relevant to the pathophysiology of psychiatric diseases.
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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 | 0.001 |
| 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) | 0.001 | 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".