8XAX

Cryo-EM structure of an anti-phage defense complex bound to AMPPNP and DNA at state 2

This is a non-PDB format compatible entry.

Summary for 8XAX

• Entry DOI: 10.2210/pdb8xax/pdb
• EMDB information: 38206
• Descriptor: ATP-binding protein, DUF4297, S20DNA1, ... (7 entities in total)
• Functional Keywords: hera, helicase duf4297, endonuclease, dna binding protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 20
• Total formula weight: 991723.14

Authors

An, Q.,Deng, Z. (deposition date: 2023-12-05, release date: 2024-06-05, Last modification date: 2024-08-14)

Primary citation

An, Q.,Wang, Y.,Tian, Z.,Han, J.,Li, J.,Liao, F.,Yu, F.,Zhao, H.,Wen, Y.,Zhang, H.,Deng, Z.
Molecular and structural basis of an ATPase-nuclease dual-enzyme anti-phage defense complex.
Cell Res., 34:545-555, 2024

PubMed Abstract: Coupling distinct enzymatic effectors emerges as an efficient strategy for defense against phage infection in bacterial immune responses, such as the widely studied nuclease and cyclase activities in the type III CRISPR-Cas system. However, concerted enzymatic activities in other bacterial defense systems are poorly understood. Here, we biochemically and structurally characterize a two-component defense system DUF4297-HerA, demonstrating that DUF4297-HerA confers resistance against phage infection by cooperatively cleaving dsDNA and hydrolyzing ATP. DUF4297 alone forms a dimer, and HerA alone exists as a nonplanar split spiral hexamer, both of which exhibit extremely low enzymatic activity. Interestingly, DUF4297 and HerA assemble into an approximately 1 MDa supramolecular complex, where two layers of DUF4297 (6 DUF4297 molecules per layer) linked via inter-layer dimerization of neighboring DUF4297 molecules are stacked on top of the HerA hexamer. Importantly, the complex assembly promotes dimerization of DUF4297 molecules in the upper layer and enables a transition of HerA from a nonplanar hexamer to a planar hexamer, thus activating their respective enzymatic activities to abrogate phage infection. Together, our findings not only characterize a novel dual-enzyme anti-phage defense system, but also reveal a unique activation mechanism by cooperative complex assembly in bacterial immunity.

PubMed: 38834762
DOI: 10.1038/s41422-024-00981-w

Experimental method

ELECTRON MICROSCOPY (2.92 Å)