9U49

crystal structure of Cdn1 in complex with cA4

9U49 の概要

• エントリーDOI: 10.2210/pdb9u49/pdb
• 関連するPDBエントリー: 8Z4I
• 分子名称: CARF-domain containing dual-activated nuclease, cyclic tetra-adenosine monophosphate(cA4), MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: complex, carf, rna binding protein/rna, rna binding protein-rna complex
• 由来する生物種: Psychrobacter lutiphocae DSM 21542; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 94061.63

構造登録者

Zhang, W. (登録日: 2025-03-19, 公開日: 2026-02-04)

主引用文献

Zhang, W.,Kong, J.,Zeng, Y.,Su, Y.,Zhang, S.,Li, Y.,Hu, C.,Chen, Q.,Xiao, Y.,Lu, M.
Structural plasticity enables broad cAn binding and dual activation of CRISPR-associated ribonuclease Cdn1.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: Prokaryotes have naturally evolved diverse RNA-guided defense systems against viral infections, with the type III CRISPR-Cas systems representing the most intricate. These systems feature accessory proteins activated by cyclic oligoadenylates (cOAs) produced upon target RNA recognition, synergizing with the CRISPR-Cas machinery to defend against exogenous invaders. Typically, each accessory protein is activated by only one specific cOA type. Here, we characterize Cdn1, a type III-B CRISPR accessory protein from Psychrobacter lutiphocae, which binds to cA3, cA4, and cA6, but activated by cA4 and cA6 with different efficacies to catalyze ssRNA cleavage. Combined structural and biochemical analyses reveal that cOA binding triggers dramatic conformational reorganization, including the formation of a dimerization interface of nuclease domains, the emergence of substrate binding cleft, and the reconstruction of a metal-dependent catalytic center essential for RNA cleavage. This dual activation mechanism illustrates evolutionary innovation within CRISPR-associated Rossman-fold nucleases. We propose that such structural plasticity evolved to maximize defensive resilience during microbial competition and horizontal gene transfer, while preserving broad-spectrum antiviral ability. These findings not only elucidate the activation mechanisms of Cdn1 within the type III systems but also underscore the functional complexity and adaptability of CRISPR-Cas ancillary proteins.

PubMed: 41569151
DOI: 10.1093/nar/gkaf1524

実験手法

X-RAY DIFFRACTION (1.9 Å)