9C5X
Molecular basis for HerA-Duf supramolecular complex in anti-phage defense - Assembly 3
This is a non-PDB format compatible entry.
Summary for 9C5X
| Entry DOI | 10.2210/pdb9c5x/pdb |
| EMDB information | 45234 |
| Descriptor | DUF4297 domain-containing protein, ATP-binding protein (2 entities in total) |
| Functional Keywords | oligomerization domain, nuclease, topoisomerase, antiviral protein |
| Biological source | Bacillus sp. HMF5848 More |
| Total number of polymer chains | 18 |
| Total formula weight | 1019061.56 |
| Authors | |
| Primary citation | Rish, A.D.,Fosuah, E.,Shen, Z.,Marathe, I.A.,Wysocki, V.H.,Fu, T.M. Architecture remodeling activates the HerA-DUF anti-phage defense system. Mol.Cell, 85:1189-1201.e5, 2025 Cited by 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 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. PubMed: 40010344DOI: 10.1016/j.molcel.2025.02.001 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.01 Å) |
Structure validation
Download full validation report
