9LQ8

Cryo-EM structure of CTR-bound type III-B CRISPR-Cas effector complex

Summary for 9LQ8

• Entry DOI: 10.2210/pdb9lq8/pdb
• EMDB information: 63296
• Descriptor: Cmr1, S-ADENOSYLMETHIONINE, MANGANESE (II) ION, ... (11 entities in total)
• Functional Keywords: crispr-cas complex, adaptive immunity, rna degradation, second messenger, immune system/rna, immune system-rna complex
• Biological source: Bacteroides fragilis; More
• Total number of polymer chains: 11
• Total formula weight: 367144.83

Authors

Jin, X.,Duan, B.,Chen, Z.,Zhao, B. (deposition date: 2025-01-28, release date: 2025-11-26, Last modification date: 2026-06-10)

Primary citation

Duan, B.,Jin, X.,An, X.,Xiao, Y.,Yang, Q.,Zhao, H.,Huang, Y.,Wang, J.,Wang, Q.,Du, F.,Lu, L.,Sun, L.,Chen, Z.,Zhao, B.
Molecular basis of SAM-AMP synthesis and degradation in the type III-B CRISPR-Cas system.
Nat.Chem.Biol., 2025

PubMed Abstract: Upon sensing nonself target RNA, the CorA-associated type III-B CRISPR-Cas system catalyzes S-adenosyl methionine (SAM) and ATP to synthesize SAM-AMP, which activates the effector CorA and triggers immune responses. SAM-AMP can be degraded by NrN and SAM lyase, potentially deactivating the system. Here we find that the type III-B effector complex from Bacteroides fragilis uses a specific mechanism to recognize nonself target RNA and synthesize SAM-AMP. The 3' anti-tag of nonself target RNA induces conformational changes in the Cmr2 subunit, triggering SAM-AMP synthesis independently of the stalk loop of Cmr3 subunit. SAM-AMP binding induces NrN to transit from an open to a closed conformation, enabling hydrolysis of the 3'-5' phosphodiester bond. SAM lyase forms a triangular trimer that specifically degrades SAM-AMP into 5'-methylthioadenosine-AMP and homoserine lactone. These findings unveil unique mechanisms for SAM-AMP synthesis and degradation and provide deeper insights into the molecular basis of type III CRISPR-Cas signaling.

PubMed: 41272318
DOI: 10.1038/s41589-025-02075-z

Experimental method

ELECTRON MICROSCOPY (2.85 Å)