9DBH

Structure of Hailong HalB in complex with oligodeoxyadenylate

9DBH の概要

• エントリーDOI: 10.2210/pdb9dbh/pdb
• 分子名称: HalB, DNA (5'-D(P*AP*AP*AP*AP*AP*A)-3'), MANGANESE (II) ION, ... (7 entities in total)
• 機能のキーワード: hailong, nucleotidyltransferase, oligodeoxyadenylate, anti-phage defense, antiviral protein, antiviral protein-dna complex, antiviral protein/dna
• 由来する生物種: Rhodobacteraceae bacterium QY30; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 111749.08

構造登録者

Tan, J.M.J.,Melamed, S.,Cofsky, J.C.,Hobbs, S.J.,Kruse, A.C.,Sorek, R.,Kranzusch, P.J. (登録日: 2024-08-23, 公開日: 2025-05-07, 最終更新日: 2025-11-19)

主引用文献

Tan, J.M.J.,Melamed, S.,Cofsky, J.C.,Syangtan, D.,Hobbs, S.J.,Del Marmol, J.,Jost, M.,Kruse, A.C.,Sorek, R.,Kranzusch, P.J.
A DNA-gated molecular guard controls bacterial Hailong anti-phage defence.
Nature, 643:794-800, 2025

PubMed Abstract: Animal and bacterial cells use nucleotidyltransferase (NTase) enzymes to respond to viral infection and control major forms of immune signaling including cGAS-STING innate immunity and CBASS anti-phage defence. Here we discover a family of bacterial defence systems, which we name Hailong, that use NTase enzymes to constitutively synthesize DNA signals and guard against phage infection. Hailong protein B (HalB) is an NTase that converts deoxy-ATP into single-stranded DNA oligomers. A series of X-ray crystal structures define a stepwise mechanism of HalB DNA synthesis initiated by a C-terminal tyrosine residue that enables de novo enzymatic priming. We show that HalB DNA signals bind to and repress activation of a partnering Hailong protein A (HalA) effector complex. A 2.0 Å cryo-EM structure of the HalA-DNA complex reveals a membrane protein with a conserved ion channel domain and a unique crown domain that binds the DNA signal and gates activation. Analyzing Hailong defence in vivo, we demonstrate that viral DNA exonucleases required for phage replication trigger release of the primed HalA complex and induce protective host cell growth arrest. Our results explain how inhibitory nucleotide immune signals can serve as molecular guards against phage infection and expand the mechanisms NTase enzymes use to control antiviral immunity.

PubMed: 40306316
DOI: 10.1038/s41586-025-09058-z

実験手法

X-RAY DIFFRACTION (1.88 Å)