Similar but Different: RBR E3 Ligases and their Domains that are Crucial for Function
Bibliographic record
Abstract
Background: The E3 ubiquitin ligases can be subdivided into four distinct types (RING, HECT, U-box, and RBR type) based on their domain architecture and ubiquitin transfer mechanism. Recent structures of different RBR E3 ligases have been solved showing enzymes in their autoinhibited state. The only exception is HOIP/ HOIL-1L which was recently solved in its “active” conformation. This review discusses the structural and functional characteristics of three different members of the RBR E3 ubiquitin ligase family: Parkin, HOIP/HOIL-1L, and HHARI. Methods: Searches were performed using PubMed. Search term includes “RBR E3 Ligase”, “Parkin”, “HOIP/ HOIL-1L”, “HHARI”, “UbcH7”, and “E2”. In the end, 25 journal articles were selected as the foundation of this review. The structural coordinates of Parkin, HOIP, and HHARI were accessed from the PDB (www.rcsb.org) with the PDB IDs 4ZYN, 5EDV, and 4KBL, respectively. Summary: Currently, most solved RBR E3 ligase structures are only in their inactive forms, except for HOIP/ HOIL-1L, and these inactive forms provide valuable information on how these proteins are regulated in vivo. All the RBR E3 ligases have common domains, but their structures and functions are heavily dependent on their accessory domains, which serve as regulators that orchestrate certain ubiquitin chain syntheses and play a role in the autoinhibition of RBR E3 ligases. Although these domains are structurally different, they use distinct molecular interactions to achieve the same goal. While the regulation of most RBR E3 ligases has been extensively studied, more structural studies are required to further characterize the mechanism that these enzymes use to build different ubiquitin chains. Understanding the mechanisms underlying the formation of each type of ubiquitin chain could help elucidate their functions and related pathways.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.008 | 0.003 |
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".