Suppressor of prr (Stp; gpAc.6) is a 26-amino-acid early regulatory peptide of bacteriophage T4 that binds and inhibits host Type IC DNA restriction-modification complexes such as EcoPrrI and EcoR124I, selectively abolishing their restriction endonuclease activity while sparing modification activity. In Escherichia coli hosts encoding the latent anticodon nuclease PrrC in complex with EcoPrrI, binding of Stp's conserved N-proximal 18-residue region allosterically unmasks PrrC, triggering cleavage of host tRNA(Lys) that wild-type T4 subsequently counters via its polynucleotide kinase/phosphatase (Pnkp) and RNA ligase 1 (RnlA) tRNA repair pathway. Stp is a non-catalytic effector peptide and possesses no intrinsic nuclease activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004518 nuclease activity | IEA GO_REF:0000002 | REMOVE | Summary: Erroneous InterPro2GO mapping from IPR012585 (T4 Suppressor of prr, Stp) / PF08133 (Nuclease_act); Stp is a 26-residue regulatory peptide, not a nuclease. Reason: Stp is a 26-amino-acid non-catalytic peptide that inhibits the host EcoPrrI restriction complex and allosterically activates the host PrrC anticodon nuclease; Stp itself has no catalytic nuclease activity. Supporting Evidence: file:BPT4/stp/stp-deep-research-falcon.md Stp itself is best understood as an **effector/regulator peptide**, not as the catalytic nuclease. file:BPT4/stp/stp-uniprot.txt Plays a role in the inactivation of several host DNA restriction systems including EcoprrI or EcoR124I. As a consequence, it activates the host anticodon nuclease PrrC. |
| GO:0050792 regulation of viral process | IEA GO_REF:0000002 | MODIFY | Summary: Vague InterPro2GO term that should be replaced by GO:0099018 (symbiont-mediated evasion of host restriction-modification system). Reason: Stp directly targets the host Type IC restriction-modification machinery (EcoPrrI/EcoR124I) rather than regulating an intrinsic viral process, supporting replacement with GO:0099018 already annotated to this gene. Proposed replacements: symbiont-mediated evasion of host restriction-modification system Supporting Evidence: file:BPT4/stp/stp-deep-research-falcon.md Penner et al. show that Stp **abolishes EcoPrrI restriction activity but not the cognate modification activity**, consistent with selective interference with the restriction apparatus file:BPT4/stp/stp-uniprot.txt Plays a role in the inactivation of several host DNA restriction systems including EcoprrI or EcoR124I. |
| GO:0052031 symbiont-mediated perturbation of host defense response | IEA GO_REF:0000043 | MODIFY | Summary: Broad parent process term that should be refined to the specific descendant GO:0099018 (symbiont-mediated evasion of host restriction-modification system). Reason: Stp specifically inhibits host Type IC restriction-modification systems (EcoPrrI and EcoR124I), which is captured by the descendant term GO:0099018 already present on the gene. Proposed replacements: symbiont-mediated evasion of host restriction-modification system Supporting Evidence: file:BPT4/stp/stp-deep-research-falcon.md Penner et al. show that Stp **abolishes EcoPrrI restriction activity but not the cognate modification activity**, consistent with selective interference with the restriction apparatus file:BPT4/stp/stp-uniprot.txt Plays a role in the inactivation of several host DNA restriction systems including EcoprrI or EcoR124I. |
| GO:0052170 symbiont-mediated suppression of host innate immune response | IEA GO_REF:0000043 | MODIFY | Summary: General keyword-mapped term that should be refined to GO:0099018 (symbiont-mediated evasion of host restriction-modification system). Reason: The innate host defense suppressed by Stp is the Type IC restriction-modification system, captured by the more specific descendant term GO:0099018 already annotated to this gene. Proposed replacements: symbiont-mediated evasion of host restriction-modification system Supporting Evidence: file:BPT4/stp/stp-deep-research-falcon.md Penner et al. show that Stp **abolishes EcoPrrI restriction activity but not the cognate modification activity**, consistent with selective interference with the restriction apparatus file:BPT4/stp/stp-uniprot.txt Plays a role in the inactivation of several host DNA restriction systems including EcoprrI or EcoR124I. |
| GO:0099018 symbiont-mediated evasion of host restriction-modification system | IEA GO_REF:0000043 | ACCEPT | Summary: Accurately captures the primary adaptive role of Stp in inhibiting host Type IC restriction endonucleases. Reason: Stp directly inhibits the restriction endonuclease activity of host Type IC restriction-modification enzymes including EcoPrrI and EcoR124I. Supporting Evidence: file:BPT4/stp/stp-deep-research-falcon.md Penner et al. show that Stp **abolishes EcoPrrI restriction activity but not the cognate modification activity**, consistent with selective interference with the restriction apparatus file:BPT4/stp/stp-uniprot.txt Plays a role in the inactivation of several host DNA restriction systems including EcoprrI or EcoR124I. As a consequence, it activates the host anticodon nuclease PrrC. |
Loading supporting content…
Download this section (compressed HTML)Q: Where on the EcoPrrI (HsdR2M2S1)-PrrC holoenzyme complex does the 26-residue Stp peptide bind to uncouple DNA translocation/restriction from PrrC silencing?
Q: How broadly does Stp inhibit other Type I restriction-modification families beyond Type IC (EcoPrrI and EcoR124I)?
Experiment: Determine the cryo-EM structure of the EcoPrrI-PrrC complex in the presence and absence of synthetic Stp peptide and dTTP/GTP to visualize the allosteric switch from anti-restriction to PrrC anticodon nuclease activation.
Experiment: Test synthetic Stp peptide variants systematically across purified Type IA, IB, and IC restriction-modification enzymes in vitro to map its inhibition spectrum and binding interface on HsdR/HsdM.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)