9LQF

Crystal structure of SAM lyase in complex with SAH-AMP

This is a non-PDB format compatible entry.

Summary for 9LQF

• Entry DOI: 10.2210/pdb9lqf/pdb
• Descriptor: SAM lyase, (2~{S})-4-[[(2~{S},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-4-oxidanyl-oxolan-2-yl]methylsulfanyl]-2-azanyl-butanoic acid, GLYCEROL, ... (4 entities in total)
• Functional Keywords: enzyme, sam, crispr-cas system, second messenger, immune system
• Biological source: Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)
• Total number of polymer chains: 12
• Total formula weight: 181210.07

Authors

Duan, B.,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

X-RAY DIFFRACTION (1.59 Å)