View source for 9pi4


==Poly dT bound form of Single stranded DNA-binding protein(ICP8) from Herpes simplex virus-1. Mutations: C254S, C455S==
<StructureSection load='9pi4' size='340' side='right'caption='[[9pi4]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9pi4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1 Human alphaherpesvirus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PI4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PI4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9pi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pi4 OCA], [https://pdbe.org/9pi4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pi4 RCSB], [https://www.ebi.ac.uk/pdbsum/9pi4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pi4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DNBI_HHV11 DNBI_HHV11] Plays several crucial roles in viral infection. Participates in the opening of the viral DNA origin to initiate replication by interacting with the origin-binding protein UL9. May disrupt loops, hairpins and other secondary structures present on ssDNA to reduce and eliminate pausing of viral DNA polymerase at specific sites during elongation. Promotes viral DNA recombination by performing strand-transfer, characterized by the ability to transfer a DNA strand from a linear duplex to a complementary single-stranded DNA circle. Can also catalyze the renaturation of complementary single strands.<ref>PMID:15078942</ref> <ref>PMID:7961904</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The HSV-1 single-strand annealing protein ICP8 (UL29) is essential for viral DNA replication and recombination. Although its overall architecture has been described, the molecular basis of single-stranded DNA (ssDNA) recognition was unknown. We report crystal structures of C-terminally truncated ICP8 (ICP8Delta60) bound to poly(dT)25 or poly(dA)25 ssDNA at 3.0-3.1 A resolution, along with higher-resolution apo structures of surface-entropy-reduction variants. ssDNA binds within the neck region between the head and shoulder domains, contacting conserved OB-fold residues via base-specific hydrogen bonds, pi-stacking and phosphate backbone interactions. In the poly(dT)25 complex, coordination of a Zn(2+) ion stabilizes the zinc finger motif; whereas, in the poly(dA)25 complex, Zn(2+) displacement promotes disulfide bond formation that effectively locks the protein into an altered conformation. Microscale thermophoresis and label-free differential scanning fluorimetry reveal a strong preference for pyrimidine-rich sequences, with nanomolar affinity for poly(dT)25 and micromolar for poly(dA)25. Structural modeling identified Y543, R576, R772, R793, Y988, and F998 as key DNA-contact residues. Alanine substitutions caused severe replication defects, particularly for R772A, Y988A, and F998A. ssDNA binding induces approximately 26 A displacement and approximately 35 degree rotation of the C-terminal domain and ordering of flexible loops, suggesting a mechanism for cooperative filament assembly. These structures define the molecular determinants of ICP8-ssDNA recognition, reveal thymidine bias and provide a framework for targeting ICP8-mediated functions in herpesvirus replication.

The crystal structure of the herpes virus ICP8 protein in complex with single-stranded DNA reveals the molecular determinants of nucleotide recognition.,Erlandsen H, Krucinska J, Wilderman PR, Makkay AM, Szczepaniak R, Wright LR, Weller SK, Wright DL J Biol Chem. 2026 Mar 13:111366. doi: 10.1016/j.jbc.2026.111366. PMID:41833734<ref>PMID:41833734</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9pi4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Human alphaherpesvirus 1]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Erlandsen H]]
[[Category: Krucinska J]]
[[Category: Wright D]]