The molecular basis of Hsp70-sulfogalactolipid binding: structure/function of protein and glycolipid components
Bibliographic record
Abstract
Heat shock/stress proteins of the 70 kD (hsp70) family have been implicated in mediating bacterial/host and sperm/egg interactions via a novel binding-specificity to the sulfated galactolipids (SGL), 3′sulfogalactosylceramide (SGC) and 3′sulfogalactosylglycerolipid(SGG). To investigate the molecular mechanism(s) of sulfated glycolipid recognition by hsp70 we have used a series of sulfated galactolipid derivatives and the recombinant testis-specific hsp70.2 gene product, rP70, as our model system. Thin layer chromatography (tlc) and receptor ELISAs demonstrated rP70 to bind specifically 3′ and 4′ sulfated galactolipids and not any other sulfated or sialic acid containing lipid. Binding to 3 ′SGL was dependent upon a ceramide-based backbone, whereas binding to 4′SGL was observed with either a ceramide or alkyhydrocarbon backbone. Binding of rP70 was not observed to the sulfated sugars heparin or 3′ sulfogalactose, suggesting that the lipid moiety and the sulfate position around the galactose ring of SGL contribute to this specific recognition event. Soluble analogues of SGC consisting of an acyl chain substitution with adamantane and a neoglycoconjugate of SGC and bovine serum albumin have both been demonstrated to function as receptors for rP70, while adamantyl-SGC inhibits rP70/SGL binding in the μM range. Proteolytic cleavage and truncation analysis demonstrated that the SGL binding site is localized within amino acids 300–387 of the highly conserved N-terminal ATPase domain of rP70. Site directed mutagenesis showed arginine 342 and phenylalanine 198 to be critical for SGL binding. Interestingly, these amino acids are conserved among all members of the hsp70 family and the ability to bind SGC/SGG is maintained among recombinant hsp70s from the bacterial pathogens, Chlamydia trachomatis , mycoplasma, Helicobacter pylori and Haemophilus influenzae. DnaK, the most widely studied intracellular chaperone also possesses SGC/SGG binding specificity. The recombinant sea urchin receptor for sperm, a member of the hsp110 family possessing 45% homology with P70, also binds SGC and SGG, extending the role of hsp70-mediated SGL recognition originally proposed in sperm/egg binding. Elucidating the molecular mechanisms of SGL recognition by hsp70 provides the basis for the rational design of specific protein, glycolipid and neogylcoconjugate compounds that may be effective in inhibiting the hsp70 adhesin function.
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) | 0.000 | 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 | 0.001 |
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".