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-Structure paper
タイトル | Assembly-mediated activation of the SIR2-HerA supramolecular complex for anti-phage defense. |
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ジャーナル・号・ページ | Mol Cell, Vol. 83, Issue 24, Page 4586-44599.e5, Year 2023 |
掲載日 | 2023年12月21日 |
著者 | Zhangfei Shen / Qingpeng Lin / Xiao-Yuan Yang / Elizabeth Fosuah / Tian-Min Fu / |
PubMed 要旨 | SIR2-HerA, a bacterial two-protein anti-phage defense system, induces bacterial death by depleting NAD upon phage infection. Biochemical reconstitution of SIR2, HerA, and the SIR2-HerA complex ...SIR2-HerA, a bacterial two-protein anti-phage defense system, induces bacterial death by depleting NAD upon phage infection. Biochemical reconstitution of SIR2, HerA, and the SIR2-HerA complex reveals a dynamic assembly process. Unlike other ATPases, HerA can form various oligomers, ranging from dimers to nonamers. When assembled with SIR2, HerA forms a hexamer and converts SIR2 from a nuclease to an NAD hydrolase, representing an unexpected regulatory mechanism mediated by protein assembly. Furthermore, high concentrations of ATP can inhibit NAD hydrolysis by the SIR2-HerA complex. Cryo-EM structures of the SIR2-HerA complex reveal a giant supramolecular assembly up to 1 MDa, with SIR2 as a dodecamer and HerA as a hexamer, crucial for anti-phage defense. Unexpectedly, the HerA hexamer resembles a spiral staircase and exhibits helicase activities toward dual-forked DNA. Together, we reveal the supramolecular assembly of SIR2-HerA as a unique mechanism for switching enzymatic activities and bolstering anti-phage defense strategies. |
リンク | Mol Cell / PubMed:38096827 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.83 - 3.6 Å |
構造データ | EMDB-40762, PDB-8su9: EMDB-40763, PDB-8sub: EMDB-40778, PDB-8suw: EMDB-40860, PDB-8sxx: EMDB-42061, PDB-8uae: EMDB-42062, PDB-8uaf: |
化合物 | ChemComp-AR6: ChemComp-ADP: ChemComp-MG: ChemComp-NAD: ChemComp-AGS: |
由来 |
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キーワード | IMMUNE SYSTEM / HerA / SIR2 / NADase / ATPase / Anti-phage system / Anti-phage / Nuclease |