Nucleoid disruption protein (Ndd; gpD2b) is a 151-amino-acid early effector protein of bacteriophage T4 that binds double-stranded DNA and rapidly remodels the architecture of the Escherichia coli host nucleoid within 2 to 3 minutes of infection. Without cleaving or degrading DNA, Ndd disorganizes the central bacterial chromosome and relocalizes host DNA toward the inner membrane periphery, thereby arresting host chromosomal DNA replication and segregating host chromatin prior to nucleolytic degradation by DenA and DenB.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IEA GO_REF:0000043 | MODIFY | Summary: Correct parent term that should be refined to GO:0003690 (double-stranded DNA binding). Reason: Biochemical assays demonstrate that Ndd binds specifically to double-stranded DNA and does not bind single-stranded DNA, supporting refinement to the descendant term GO:0003690 (double-stranded DNA binding). Proposed replacements: double-stranded DNA binding Supporting Evidence: file:BPT4/ndd/ndd-deep-research-falcon.md function as a **structural bridge** between DNA and membrane file:BPT4/ndd/ndd-uniprot.txt Binds to dsDNA but not to ssDNA. {ECO:0000269|PubMed:9748458}. |
| GO:0044071 symbiont-mediated perturbation of host cell cycle progression | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Downstream consequence of nucleoid disruption and host DNA replication arrest rather than direct regulation of the cell division machinery. Reason: Ndd disrupts the bacterial nucleoid and blocks host chromosomal DNA replication (GO:0098673), which secondarily prevents normal bacterial cell cycle progression and nucleoid segregation. Supporting Evidence: file:BPT4/ndd/ndd-deep-research-falcon.md short-term expression of bacteriophage T4 **Ndd** disrupted the nucleoid and relocalized it toward the **inner membrane/periphery** file:BPT4/ndd/ndd-uniprot.txt Disorganizes the host nucleoid and inhibits replication, but without host DNA cleavage or degradation. Only the architecture of the nucleoid is affected. |
| GO:0098673 symbiont-mediated suppression of host DNA replication | IEA GO_REF:0000043 | ACCEPT | Summary: Accurately captures the core biological process mediated by Ndd during early T4 infection. Reason: Ndd-induced disorganization and peripheral relocalization of the host nucleoid directly inhibits host chromosomal DNA replication independently of host DNA cleavage. Supporting Evidence: file:BPT4/ndd/ndd-deep-research-falcon.md The best-supported functional annotation for T4 Ndd is that it is an **early infection effector** that causes rapid **host nucleoid disruption/redistribution**, a hallmark phenotype beginning **~2–3 minutes** after infection file:BPT4/ndd/ndd-uniprot.txt Disorganizes the host nucleoid and inhibits replication, but without host DNA cleavage or degradation. |
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Download this section (compressed HTML)Q: Does Ndd tether host chromosomal DNA directly to the Escherichia coli inner membrane or via interaction with a specific host inner-membrane protein or nucleoid-associated protein?
Q: Does Ndd distinguish unmodified cytosine-containing host DNA from 5-hydroxymethylcytosine-containing T4 DNA?
Experiment: Perform ChIP-seq and Hi-C in Escherichia coli expressing T4 Ndd to map whether Ndd binds specific chromosomal macrodomains or architectural motifs during nucleoid peripheralization.
Experiment: Compare Ndd binding affinity for unmodified cytosine dsDNA versus 5hmC-modified and glucosylated-5hmC dsDNA using fluorescence anisotropy and surface plasmon resonance.
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