9IAC

Structure of the Argonaute-associated Cas4 family protein 1 (ACE1) from Microcystis aeruginosa (MaACE1)

Summary for 9IAC

• Entry DOI: 10.2210/pdb9iac/pdb
• Related: 9IAB
• Descriptor: Similar to tr|Q3MCC8|Q3MCC8_ANAVT Hypothetical protein, IRON/SULFUR CLUSTER, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: cas4 family protein, immune system, deoxyribonuclease, hydrolase
• Biological source: Microcystis aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 65252.70

Authors

Bobadilla Ugarte, P.,Halter, S.,Jinek, M.,Swarts, D.C. (deposition date: 2025-02-09, release date: 2025-04-23, Last modification date: 2025-05-28)

Primary citation

Bobadilla Ugarte, P.,Halter, S.,Mutte, S.K.,Heijstek, C.,Niault, T.,Terenin, I.,Barendse, P.,Koopal, B.,Roosjen, M.,Boeren, S.,Hauryliuk, V.,Jinek, M.,Westphal, A.H.,Swarts, D.C.
Cyanobacterial Argonautes and Cas4 family nucleases cooperate to interfere with invading DNA.
Mol.Cell, 85:1920-, 2025

PubMed Abstract: Prokaryotic Argonaute proteins (pAgos) from the long-A clade are stand-alone immune systems that use small interfering DNA (siDNA) guides to recognize and cleave invading plasmid and virus DNA. Certain long-A pAgos are co-encoded with accessory proteins with unknown functions. Here, we show that cyanobacterial long-A pAgos act in conjunction with Argonaute-associated Cas4 family enzyme 1 (ACE1). Structural and biochemical analyses reveal that ACE1-associated pAgos mediate siDNA-guided DNA interference, akin to stand-alone pAgos. ACE1 is structurally homologous to the nuclease domain of bacterial DNA repair complexes and acts as a single-stranded DNA endonuclease that processes siDNA guides. pAgo and ACE1 form a heterodimeric long-A pAgo-ACE1 (APACE1) complex, which modulates ACE1 activity. Although ACE1-associated pAgos alone interfere with plasmids and bacteriophages, plasmid interference is boosted when pAgo and ACE1 are co-expressed. Our study reveals that pAgo-mediated immunity is enhanced by accessory proteins and broadens our mechanistic understanding of how pAgo systems interfere with invading DNA.

PubMed: 40288374
DOI: 10.1016/j.molcel.2025.03.025

Experimental method

X-RAY DIFFRACTION (2.52 Å)