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Now I'll review the GO-CAM model with ID "62b4ffe300003618".

GO-CAM Review: Poxvirus-OPG045 inhibition of host BAK-mediated apoptosis (Human-Poxvirus)

Model ID: gomodel:62b4ffe300003618

Summary

This GO-CAM model describes the inhibition of host BAK-mediated apoptosis by the vaccinia virus protein OPG045 (also known as F1L). The model captures key molecular functions and causal relationships in the intrinsic apoptotic pathway and how it is inhibited by the viral protein.

Biological Content Assessment

The model accurately represents a well-documented biological mechanism: vaccinia virus protein F1L (OPG045) disrupts host apoptosis by directly binding to and inhibiting the pro-apoptotic host protein BAK, preventing its activation and subsequent steps in the intrinsic apoptotic pathway.

The model includes four main activities: 1. OPG045/F1L's protein sequestering activity (inhibiting BAK) 2. BAK1's porin activity at the mitochondrial outer membrane 3. CASP9's cysteine-type endopeptidase activity in mitochondria 4. CASP3's cysteine-type endopeptidase activity in cytoplasm

Accuracy of Molecular Functions and Interactions

The model accurately represents the molecular mechanism based on the literature:

  • OPG045 (F1L) activity: Correctly annotated with "protein sequestering activity" (GO:0140311) occurring in mitochondria. This is well-established in the literature (PMID:16439990), which shows F1L directly binds to BAK via its BH3 domain to prevent BAK activation.

  • BAK1 activity: Appropriately annotated with "porin activity" (GO:0015288) at the mitochondrial outer membrane, which is part of the intrinsic apoptotic pathway (GO:0097193).

  • Causal relationships: The inhibitory action of OPG045 on BAK (RO:0002630 - directly negatively regulates) is accurate, as is BAK's positive regulation of CASP9 (RO:0002304 - causally upstream of, positive effect) and CASP9's positive regulation of CASP3 (RO:0002629 - directly positively regulates).

Literature Validation

The molecular functions and interactions captured in the model are strongly supported by the literature:

  • PMID:22006182 demonstrates that BAK functions as a mitochondrial porin, forming holes in the outer membrane during apoptosis.

  • PMID:16439990 clearly establishes that F1L/OPG045 binds to BAK via a BH3-like domain, preventing BAK activation and subsequent apoptosis.

Ontology and Curation Assessment

Correct Use of GO Terms and Relations

The model uses appropriate GO terms for the molecular functions and biological processes:

  • GO:0140311 (protein sequestering activity) is the correct term for OPG045's function
  • GO:0015288 (porin activity) correctly describes BAK1's role
  • GO:0004197 (cysteine-type endopeptidase activity) is appropriate for both CASP9 and CASP3
  • GO:0033668 (symbiont-mediated suppression of host apoptosis) correctly represents the viral process

The causal relationships use appropriate relation ontology (RO) terms: - RO:0002630 (directly negatively regulates) correctly represents OPG045's inhibition of BAK - RO:0002304 (causally upstream of, positive effect) correctly shows BAK's effect on CASP9 - RO:0002629 (directly positively regulates) correctly shows CASP9's activation of CASP3

Model Structure and Organization

The model structure is well-organized, showing a clear pathway from viral inhibition to downstream effects in the apoptotic pathway. The model follows the GO-CAM best practices for representing molecular activities connected by causal relationships.

Complex Representation

The model does not include protein complexes, which is appropriate for this particular mechanism, as the interactions described involve direct protein-protein interactions rather than complex formation activities. According to the GO-CAM guidelines for complexes (referenced in "How_to_annotate_complexes_in_GO-CAM"), this model correctly focuses on the specific proteins and their activities rather than complexes.

Improvement Suggestions

While the model is generally well-constructed, a few minor additions or clarifications could enhance it:

  1. Additional BAK oligomerization detail: The model could potentially include BAK's homo-oligomerization process that occurs during apoptosis, which is mentioned in PMID:22006182. This would add detail to how BAK forms pores in the mitochondrial membrane.

  2. BAX representation: The literature indicates that BAK and BAX have functionally redundant roles in apoptosis. The model could potentially include BAX to provide a more complete picture of the intrinsic apoptotic pathway and how F1L might differentially affect BAK vs. BAX.

  3. Cytochrome c release: The model could be extended to include the release of cytochrome c from mitochondria, which is a key consequence of BAK/BAX pore formation and a trigger for apoptosome formation and caspase activation.

Conclusion

This GO-CAM model (gomodel:62b4ffe300003618) is a high-quality representation of how vaccinia virus protein OPG045/F1L inhibits host apoptosis by directly targeting BAK. The model accurately captures the molecular functions, subcellular locations, and causal relationships supported by the literature. It effectively illustrates a key viral mechanism for evading host cell death.

The model follows GO-CAM best practices in terms of ontology usage and representation of biological processes. With a few minor enhancements as suggested, it could provide an even more comprehensive picture of this important host-pathogen interaction.