9NHC

Cryo-EM structure of SIWI-piRNA-target(49-nt)-GTSF1-Maelstrom complex

Summary for 9NHC

• Entry DOI: 10.2210/pdb9nhc/pdb
• Related: 9NHB
• EMDB information: 49408
• Descriptor: Piwi-like protein Siwi, piRNA, target RNA (49-nt), ... (7 entities in total)
• Functional Keywords: siwi, gtsf1, maelstrom, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Bombyx mori (domestic silkworm); More
• Total number of polymer chains: 5
• Total formula weight: 192703.74

Authors

Sarkar, S.,Gebert, L.F.R.,MacRae, I.J. (deposition date: 2025-02-24, release date: 2025-09-17, Last modification date: 2025-10-01)

Primary citation

De, D.,Sarkar, S.,Gebert, L.F.R.,Wiryaman, T.,Anzelon, T.A.,MacRae, I.J.
A conserved PIWI silencing complex detects piRNA-target engagement.
Mol.Cell, 85:3275-3287.e7, 2025

PubMed Abstract: In animal germ cells, PIWI proteins use piRNAs to detect active selfish genetic elements. Base-pairing to a piRNA defines transposon recognition, but how this interaction triggers a defensive response remains unclear. Here, we identify a transposon recognition complex composed of the silkworm proteins Siwi, GTSF1, and Maelstrom. Biochemical and cryo-electron microscopy (cryo-EM) analyses show that extended piRNA-target pairing locks Siwi in a conformation that recruits GTSF1 and Maelstrom. Extended piRNA-target pairing is recognized by the N-terminal helix of Maelstrom and the first zinc finger of GTSF1, which act together to hold Siwi in an endonucleolytically active state. The resulting activated complex, termed Siwi, rapidly cleaves target RNAs and recruits the piRNA biogenesis factor Spindle-E. Structural predictions reveal related complexes in animals ranging from humans to sponges, indicating PIWI assembly is a conserved transposon recognition mechanism employed broadly across the metazoan kingdom.

PubMed: 40912244
DOI: 10.1016/j.molcel.2025.08.010

Experimental method

ELECTRON MICROSCOPY (3.6 Å)