9C6A

The CRISPR associated adenosine deaminase Cad1-CARF in the apo form

9C6A の概要

• エントリーDOI: 10.2210/pdb9c6a/pdb
• 分子名称: Adenosine deaminase domain-containing protein (2 entities in total)
• 機能のキーワード: type-iii crispr defense system, carf-effector protein, adaptive immunity, deamination defense strategy, cytosolic protein
• 由来する生物種: Bacteroidales bacterium
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75862.78

構造登録者

Majumder, P.,Patel, D.J. (登録日: 2024-06-07, 公開日: 2024-10-30, 最終更新日: 2024-12-25)

主引用文献

Baca, C.F.,Majumder, P.,Hickling, J.H.,Ye, L.,Teplova, M.,Brady, S.F.,Patel, D.J.,Marraffini, L.A.
The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity.
Cell, 187:7183-, 2024

PubMed Abstract: Type III CRISPR systems provide immunity against genetic invaders through the production of cyclic oligo-adenylate (cA) molecules that activate effector proteins that contain CRISPR-associated Rossman fold (CARF) domains. Here, we characterized the function and structure of an effector in which the CARF domain is fused to an adenosine deaminase domain, CRISPR-associated adenosine deaminase 1 (Cad1). We show that upon binding of cA or cA to its CARF domain, Cad1 converts ATP to ITP, both in vivo and in vitro. Cryoelectron microscopy (cryo-EM) structural studies on full-length Cad1 reveal an hexameric assembly composed of a trimer of dimers, with bound ATP at inter-domain sites required for activity and ATP/ITP within deaminase active sites. Upon synthesis of cA during phage infection, Cad1 activation leads to a growth arrest of the host that prevents viral propagation. Our findings reveal that CRISPR-Cas systems employ a wide range of molecular mechanisms beyond nucleic acid degradation to provide adaptive immunity in prokaryotes.

PubMed: 39471810
DOI: 10.1016/j.cell.2024.10.002

実験手法

X-RAY DIFFRACTION (3.6 Å)