8ZU6
Solution NMR Structure of PACT D3 Homodimer
Summary for 8ZU6
| Entry DOI | 10.2210/pdb8zu6/pdb |
| Descriptor | Interferon-inducible double-stranded RNA-dependent protein kinase activator A (1 entity in total) |
| Functional Keywords | dsrna-binding protein, protein binding |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 20542.71 |
| Authors | |
| Primary citation | Ahmad, S.,Zou, T.,Hwang, J.,Zhao, L.,Wang, X.,Davydenko, A.,Buchumenski, I.,Zhuang, P.,Fishbein, A.R.,Capcha-Rodriguez, D.,Orgel, A.,Levanon, E.Y.,Myong, S.,Chou, J.,Meyerson, M.,Hur, S. PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration. Nat Commun, 16:3325-3325, 2025 Cited by PubMed Abstract: The innate immune sensor PKR for double-stranded RNA (dsRNA) is critical for antiviral defense, but its aberrant activation by cellular dsRNA is linked to various diseases. The dsRNA-binding protein PACT plays a critical yet controversial role in this pathway. We show that PACT directly suppresses PKR activation by endogenous dsRNA ligands, such as inverted-repeat Alu RNAs, which robustly activate PKR in the absence of PACT. Instead of competing for dsRNA binding, PACT prevents PKR from scanning along dsRNA-a necessary step for PKR molecules to encounter and phosphorylate each other for activation. While PKR favors longer dsRNA for increased co-occupancy and scanning-mediated activation, longer dsRNA is also more susceptible to PACT-mediated regulation due to increased PACT-PKR co-occupancy. Unlike viral inhibitors that constitutively suppress PKR, this RNA-dependent mechanism allows PACT to fine-tune PKR activation based on dsRNA length and quantity, ensuring self-tolerance without sequestering most cellular dsRNA. PubMed: 40199855DOI: 10.1038/s41467-025-58433-x PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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