Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | The herpes simplex origin-binding protein: mechanisms for sequence-specific DNA binding and dimerization revealed by Cryo-EM. |
|---|---|
| Journal, issue, pages | Nucleic Acids Res, Vol. 53, Issue 19, Year 2025 |
| Publish date | Oct 14, 2025 |
 Authors | Emil Gustavsson / Kay Grünewald / Per Elias / B Martin Hällberg /   |
| PubMed Abstract | Herpes simplex viruses 1 and 2 (HSV-1,2) present growing treatment challenges due to increasing resistance to antivirals targeting viral DNA polymerase, particularly in immunocompromised individuals. ...Herpes simplex viruses 1 and 2 (HSV-1,2) present growing treatment challenges due to increasing resistance to antivirals targeting viral DNA polymerase, particularly in immunocompromised individuals. The HSV-1 origin-binding protein (OBP), an essential Superfamily 2 (SF2) DNA helicase encoded by the UL9 gene, is a promising alternative therapeutic target. Here, we present cryo-EM structures of OBP at up to 2.8 Å resolution in multiple conformational states, including complexes with the OriS recognition sequence and the non-hydrolyzable ATP analog ATPγS. The structures reveal an unexpected head-to-tail dimer stabilized by the C-terminal domain, where the conserved RVKNL motif mediates sequence-specific DNA recognition. The C-terminal domain extends into the partner monomer, suggesting a regulatory mechanism involving the single-stranded DNA-binding protein ICP8. We also resolve an OBP monomer bound to a DNA hairpin with a 3' single-stranded tail (mini-OriS*), and at lower resolution, a dimer-dimer assembly of two OBP dimers bound simultaneously to OriS or mini-OriS*. These structures uncover the molecular basis of HSV-1 origin recognition and unwinding, and identify multiple druggable interfaces, laying the groundwork for structure-based antiviral development targeting HSV-1 OBP. |
 External links | Nucleic Acids Res / PubMed:41125242 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.74 - 4.38 Å |
| Structure data | EMDB-52135, PDB-9hgi:  EMDB-52136: Focused map of HSV-1 Origin Binding Protein monomer A in complex with double-stranded DNA recognition sequence OriS with 6 basepairs removed from the AT-rich region  EMDB-52137: Focused map of HSV-1 Origin Binding Protein monomer B in complex with double-stranded DNA recognition sequence OriS with 6 basepairs removed from the AT-rich region EMDB-52145, PDB-9hgj:  EMDB-52146: Composite map of HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail  EMDB-52147: Consensus map of HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail  EMDB-52148: Focused map of dimer 1 in HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail  EMDB-52149: Focused map of dimer 2 of HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail  EMDB-52150: HSV-1 Origin Binding Protein monomer in complex with hairpin DNA OriS recognition sites Box 1 and Box 3 with 10 dT-tail |
| Chemicals |  ChemComp-AGS:  ChemComp-MG: |
| Source |
|
 Keywords | DNA BINDING PROTEIN / DNA / Helicase / Complex |
human alphaherpesvirus 1 strain kos