9C6A

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

Summary for 9C6A

• Entry DOI: 10.2210/pdb9c6a/pdb
• Descriptor: Adenosine deaminase domain-containing protein (2 entities in total)
• Functional Keywords: type-iii crispr defense system, carf-effector protein, adaptive immunity, deamination defense strategy, cytosolic protein
• Biological source: Bacteroidales bacterium
• Total number of polymer chains: 4
• Total formula weight: 75862.78

Authors

Majumder, P.,Patel, D.J. (deposition date: 2024-06-07, release date: 2024-10-30, Last modification date: 2024-12-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.6 Å)