9vlq

herpes simplex virus type 1 helicase-primase structure in complex with ssDNA, ADP and magnesium ion

spinqualitylabelsall models 9vlq, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9vlq is a 4 chain structure with sequence from Human alphaherpesvirus 1 strain 17 and SsDNA virus sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: ADP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HELI_HHV11 Component of the helicase/primase complex. Unwinds the DNA at the replication forks and generates single-stranded DNA for both leading and lagging strand synthesis. The primase synthesizes short RNA primers on the lagging strand that the polymerase elongates using dNTPs. Possesses helicase-like motifs and therefore may act as the helicase subunit of the complex.[HAMAP-Rule:MF_04030] Publication Abstract from PubMed DNA unwinding and primer synthesis are fundamental processes in genome replication. The human herpes simplex virus type 1 (HSV-1) helicase-primase forms a unique heterotrimeric primosome that is essential for viral DNA unwinding and primer synthesis and represents an ideal drug target. However, its molecular mechanism remains poorly understood. Here we report the cryo-electron microscopic structure of the primosome in complex with single-stranded DNA, ADP and Mg(2+) to 3.47 A resolution, which reveals that the primosome forms an unprecedented architecture in a fully open DNA binding groove between the helicase domains 1A and 2A-2B and that the primase subunit UL52 interacts extensively with the helicase subunit UL5 and accessory protein subunit UL8. Integrating mutagenesis, biochemical assays, structural analysis and 3D variability display analysis, we have identified the active sites of the ATPase, helicase and primase and critical interfaces between UL52, UL5 and UL8. Our work suggests that the primosome unwinds and translocates DNA via bidirectional rotation, and proposes a mechanistic model for DNA-dependent ATPase activation and alternating activity between helicase and primase. Herpesviridae family viruses pose significant threats to human health worldwide, and this trimeric assembly of primosomes is conserved. Our work provides a framework for understanding replication mechanisms across related viruses and for the rational design of broad-spectrum antivirals. Structural and mechanistic insights into the herpes simplex virus type 1 helicase-primase primosome.,Wu Y, Jiang Z, Chen X, Li D, Zhang Z, Dong C Cell Discov. 2025 Dec 10;11(1):100. doi: 10.1038/s41421-025-00855-4. PMID:41372195 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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