NMR Insights Into the Structural Dynamics of p47, A Key Adaptor Protein of p97 in Golgi Reassembly
Bibliographic record
Abstract
The Golgi apparatus undergoes systematic disassembly and reassembly during the cell cycle, a process requiring membrane fusion mediated by the AAA+ ATPase p97/VCP and its adaptor p47. While the p97-p47 complex plays a pivotal role in post-mitotic Golgi reassembly, the exact molecular mechanism underlying its function has not been completely understood. In particular, the conformational flexibility and dynamic feature of p47 hinders its structural characterization by cryo-electron microscopy and X-ray crystallography. Here, using NMR spectroscopy, we characterize the conformational dynamics of p47 and investigate its intra- and intermolecular interactions. p47 consists of three folded domains connected by intrinsically disordered regions (IDRs). We show that p47 adopts a "beads-on-a-string" arrangement and identify several regions that undergo microsecond-to-millisecond timescale motions, which may have functional significance. Using paramagnetic relaxation enhancement (PRE) experiments, we capture transient inter-domain and domain-linker interactions, gaining insights into the structural organization of the domains and linkers in p47. Notably, we identify and characterize an intramolecular interaction between a SEP-interacting motif (SIM), located on the flexible linker, and the SEP domain, suggesting a conserved structural and functional feature among SEP-containing p97 adaptors. Additionally, we observed transient intermolecular interactions between p47 molecules, primarily mediated by the SEP domain. These findings provide a comprehensive view of the structural organization and dynamics of p47, shedding light on how its modular architecture and multivalent interactions may modulate p97 activity and assist Golgi membrane reassembly.
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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".