Crystal structure of the MBD domain of MBD3 in complex with methylated CG DNA
Bibliographic record
Abstract
ABSTRACT MBD3 is a core subunit of the Mi-2/NuRD complex, and has been previously reported to lack methyl-CpG binding ability. However, recent reports show that MBD3 recognizes both mCG and hmCG DNA with a preference for hmCG, and is required for the normal expression of hmCG marked genes in ES cells. Nevertheless, it is not clear how MBD3 recognizes the methylated DNA. In this study, we carried out structural analysis coupled with isothermal titration calorimetry (ITC) binding assay and mutagenesis studies to address the structural basis for the mCG DNA binding ability of the MBD3 MBD domain. We found that the MBD3 MBD domain prefers binding mCG over hmCG through the conserved arginine fingers, and this MBD domain as well as other mCG binding MBD domains can recognize the mCG duplex without orientation selectivity. Furthermore, we found that the tyrosine-to-phenylalanine substitution at Phe34 of MBD3 is responsible for its weaker mCG DNA binding ability compared to other mCG binding MBD domains. In summary, our study demonstrates that the MBD3 MBD domain is a mCG binder, and also illustrates its binding mechanism to the methylated CG DNA.
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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".