8OZC

cryoEM structure of SPARTA complex heterodimer apo

8OZC の概要

• エントリーDOI: 10.2210/pdb8ozc/pdb
• EMDBエントリー: 17299 17304
• 分子名称: TIR domain-containing protein, Piwi domain-containing protein (2 entities in total)
• 機能のキーワード: sparta, tir, prokaryotic argonaute, dna binding protein
• 由来する生物種: Maribacter polysiphoniae; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 111362.00

構造登録者

Ekundayo, B.,Ni, D.C.,Lu, X.H.,Stahlberg, H. (登録日: 2023-05-09, 公開日: 2023-08-16, 最終更新日: 2023-08-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4 Å)