Novel myristoylation of the sperm-specific hexokinase 1 isoform regulates its atypical localization
Bibliographic record
Abstract
The hexokinase 1 variant in mammalian spermatozoa (HK1S) has a unique N-terminus and this isoform atypically localizes to the plasma membrane. However, the mechanism of this process currently remains ambiguous. In this report, we show that fatty acylation underlies the specific sorting of HK1S. Employing chimeric reporter constructs, we first established that compartmentalization of HK1S does not function exclusively in sperm cells and that this feature is swappable to somatic HEK293 cells. Although the N-terminus lacks the classical consensus signature for myristoylation and the sequence-based predictions fail to predict myristoylation of HK1S, complementary experimental approaches confirmed that HK1S is myristoylated. Using live-cell confocal microscopy, we show that the mutation of a single amino acid, the myristoyl recipient Gly(2), impedes the prominent feature of plasma membrane association and relocates the enzyme to the cytosol but not the nucleus. Additionally, substitutions of the putatively palmitoylated Cys(5) is also reflected in a similar loss of compartmentalization of the protein. Taken together, our findings conclusively demonstrate that the N-terminal 'MGQICQ' motif in the unique GCS domain of HK1S acquires hydrophobicity by dual lipidic modifications, N-myristoylation and palmitoylation, to serve the requirements for membranous associations and thus its compartmentalization.
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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".