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-Structure paper
タイトル | Activation mechanism of a short argonaute-TIR prokaryotic immune system. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 29, Page eadh9002, Year 2023 |
掲載日 | 2023年7月21日 |
著者 | Dongchun Ni / Xuhang Lu / Henning Stahlberg / Babatunde Ekundayo / |
PubMed 要旨 | 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 ...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. |
リンク | Sci Adv / PubMed:37467330 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.91 - 4.85 Å |
構造データ | EMDB-17299, PDB-8oz6: EMDB-17300: Duplex-bound tetramer high-resolution (EMDB-xxxx) SPARTA complex EMDB-17301: Dimer-1 SPARTA complex EMDB-17302: Dimer-2 SPARTA complex EMDB-17303: monomer-duplex bound EMDB-17304, PDB-8ozc: EMDB-17305, PDB-8ozd: EMDB-17306, PDB-8oze: EMDB-17307, PDB-8ozf: EMDB-17308, PDB-8ozg: EMDB-17310, PDB-8ozi: |
化合物 | ChemComp-AR6: ChemComp-MG: ChemComp-NAD: |
由来 |
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キーワード | ANTIVIRAL PROTEIN / SPARTA / TIR / prokaryotic argonaute / DNA BINDING PROTEIN / IMMUNE SYSTEM |