8OZD

cryoEM structure of SPARTA complex dimer-3

Summary for 8OZD

• Entry DOI: 10.2210/pdb8ozd/pdb
• EMDB information: 17304 17305
• Descriptor: TIR domain-containing protein, Piwi domain-containing protein, RNA (18-MER), ... (4 entities in total)
• Functional Keywords: sparta, tir, prokaryotic argonaute, dna binding protein
• Biological source: Maribacter polysiphoniae; More
• Total number of polymer chains: 8
• Total formula weight: 243588.77

Authors

Ekundayo, B.,Ni, D.C.,Lu, X.H.,Stahlberg, H. (deposition date: 2023-05-09, release date: 2023-08-16, Last modification date: 2023-08-23)

Primary citation

Ni, D.,Lu, X.,Stahlberg, H.,Ekundayo, B.
Activation mechanism of a short argonaute-TIR prokaryotic immune system.
Sci Adv, 9:eadh9002-eadh9002, 2023

PubMed Abstract: Short prokaryotic argonaute (pAgo) and toll/interleukin-1 receptor/resistance protein (TIR)-analog of PAZ (APAZ) form a heterodimeric SPARTA complex that provides immunity to its prokaryotic host through an abortive infection mechanism. Monomeric SPARTA senses foreign RNA/DNA duplexes to assemble an active tetramer resulting in cell death by nicotinamide adenine dinucleotide (oxidized form) (NAD) depletion via an unknown mechanism. We report nine structures of SPARTA in different functional states at a resolution range of 4.2 to 2.9 angstroms, revealing its activation mechanism. Inactive SPARTA monomers bind to RNA/DNA duplexes to form symmetric dimers mediated by the association of Ago subunits. The initiation of tetramer assembly induces flexibility of the TIR domains enabling a symmetry-breaking rotational movement of a TIR domain in the dimer units which facilitates the TIR oligomerization, resulting in the formation of the substrate binding pocket and the activation of the SPARTA complex's NADase activity. Our findings provide detailed structural and mechanistic insights into activating a short argonaute defense system.

PubMed: 37467330
DOI: 10.1126/sciadv.adh9002

Experimental method

ELECTRON MICROSCOPY (3.89 Å)