9pi6 | pdb_00009pi6

Single stranded DNA-binding protein (ICP8) from Herpes simplex virus-1, apo form.Mutations: K166A, E167A, C254S, C455S

spinqualitylabelsall models 9pi6, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9pi6 is a 2 chain structure with sequence from Human alphaherpesvirus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.75Å Ligands: GOL, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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