9NYU

Crystal structure of KwaB dimer

Summary for 9NYU

• Entry DOI: 10.2210/pdb9nyu/pdb
• Descriptor: Kiwa protein KwaB (1 entity in total)
• Functional Keywords: antiphage, kiwa system, kwab dimer, antiviral protein
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 72294.91

Authors

Zhiying, Z.,Dinshaw, J.P. (deposition date: 2025-03-28, release date: 2025-08-06, Last modification date: 2026-05-20)

Primary citation

Zhang, Z.,Todeschini, T.C.,Wu, Y.,Kogay, R.,Naji, A.,Cardenas Rodriguez, J.,Mondi, R.,Kaganovich, D.,Taylor, D.W.,Bravo, J.P.K.,Teplova, M.,Amen, T.,Koonin, E.V.,Patel, D.J.,Nobrega, F.L.
Kiwa is a membrane-embedded defense supercomplex activated at phage attachment sites.
Cell, 188:5862-5877.e23, 2025

PubMed Abstract: Bacteria and archaea deploy diverse antiviral defense systems, many of which remain mechanistically uncharacterized. Here, we characterize Kiwa, a widespread two-component system composed of the transmembrane sensor KwaA and the DNA-binding effector KwaB. Cryogenic electron microscopy (cryo-EM) analysis reveals that KwaA and KwaB assemble into a large, membrane-associated supercomplex. Upon phage binding, KwaA senses infection at the membrane, leading to KwaB binding of ejected phage DNA and inhibition of replication and late transcription, without inducing host cell death. Although KwaB can bind DNA independently, its antiviral activity requires association with KwaA, suggesting spatial or conformational regulation. We show that the phage-encoded DNA-mimic protein Gam directly binds and inhibits KwaB but that co-expression with the Gam-targeted RecBCD system restores protection by Kiwa. Our findings support a model in which Kiwa coordinates membrane-associated detection of phage infection with downstream DNA binding by its effector, forming a spatially coordinated antiviral mechanism.

PubMed: 40730155
DOI: 10.1016/j.cell.2025.07.002

Experimental method

X-RAY DIFFRACTION (3.6 Å)