The B domain of the mitochondrial fission mechanoenzyme Drp1 is intrinsically disordered and coacervates under crowding conditions
Bibliographic record
Abstract
The Dynamin superfamily is a class of large GTPases that perform essential membrane remodeling events via self‐assembly stimulated GTP hydrolysis in a manner that involves the coordination of lipid‐membrane interaction, high‐order oligomerization, and GTP hydrolysis, however a clear understanding of how these functions are coordinated has remained elusive. A “variable domain” (VD) is present in many superfamily members and may enable specific targeting to sites of action, but the nature of VD function is unclear in most dynamins. Dynamin‐related protein 1 (Drp1) is the primary mechanoenzyme responsible for mitochondrial fission. We seek to identify the role of the Drp1 VD, or B domain. We find that removal of the B domain from Drp1 results in enhanced assembly and GTP hydrolysis, suggesting that the B domain has an auto‐inhibitory role. We find that the B domain is intrinsically disordered (ID) and surprisingly, undergoes phase separation or coacervation under conditions that induce other ID proteins to fold. The same conditions that induce phase separation of the B domain also enhance binding to cardiolipin, a lipid that is unique to the mitochondrial membrane. Based on these findings we suggest a model in which the B domain inhibit Drp1 assembly by dynamically occluding assembly interfaces, and that this auto‐inhibition is relieved upon interaction of the B domain with cardiolipin at the mitochondrial membrane, involving the process of coacervation. This model may also be applicable to other members of the dynamin superfamily, and intrinsically disordered membrane remodeling proteins in general. Support or Funding Information NIH R01‐GM067180
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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".