8ZU6

Solution NMR Structure of PACT D3 Homodimer

8ZU6 の概要

• エントリーDOI: 10.2210/pdb8zu6/pdb
• 分子名称: Interferon-inducible double-stranded RNA-dependent protein kinase activator A (1 entity in total)
• 機能のキーワード: dsrna-binding protein, protein binding
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 20542.71

構造登録者

Zhao, L.,Ahmad, S.,Hur, S.,Chou, J. (登録日: 2024-06-08, 公開日: 2025-04-16)

主引用文献

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

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: 40199855
DOI: 10.1038/s41467-025-58433-x

実験手法

SOLUTION NMR