+Search query
-Structure paper
| Title | Architecture remodeling activates the HerA-DUF anti-phage defense system. |
|---|---|
| Journal, issue, pages | Mol Cell, Vol. 85, Issue 6, Page 1189-11201.e5, Year 2025 |
| Publish date | Mar 20, 2025 |
Authors | Anthony D Rish / Elizabeth Fosuah / Zhangfei Shen / Ila A Marathe / Vicki H Wysocki / Tian-Min Fu / ![]() |
| PubMed Abstract | Leveraging AlphaFold models and integrated experiments, we characterized the HerA-DUF4297 (DUF) anti-phage defense system, focusing on DUF's undefined biochemical functions. Guided by structure-based ...Leveraging AlphaFold models and integrated experiments, we characterized the HerA-DUF4297 (DUF) anti-phage defense system, focusing on DUF's undefined biochemical functions. Guided by structure-based genomic analyses, we found DUF homologs to be universally distributed across diverse bacterial immune systems. Notably, one such homolog, Cap4, is a nuclease. Inspired by this evolutionary clue, we tested DUF's nuclease activity and observed that DUF cleaves DNA substrates only when bound to its partner protein HerA. To dissect the mechanism of DUF activation, we determined the structures of DUF and HerA-DUF. Although DUF forms large oligomeric assemblies both alone and with HerA, oligomerization alone was insufficient to elicit nuclease activity. Instead, HerA binding induces a profound architecture remodeling that propagates throughout the complex. This remodeling reconfigures DUF into an active nuclease capable of robust DNA cleavage. Together, we highlight an architecture remodeling-driven mechanism that may inform the activation of other immune systems. |
External links | Mol Cell / PubMed:40010344 |
| Methods | EM (single particle) |
| Resolution | 2.76 - 3.38 Å |
| Structure data | EMDB-45124, PDB-9c1m: EMDB-45125, PDB-9c1n: EMDB-45126, PDB-9c1o: EMDB-45132, PDB-9c1x: EMDB-45234, PDB-9c5x: |
| Source |
|
Keywords | ANTIVIRAL PROTEIN / anti-phage / nuclease / ATPase / 18-mer / Complex / topoisomerase / 12-mer / Oligomerization domain |
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors
External links










Keywords