8hlz

F8-A22-E4 complex of MPXV in hexameric form

spinqualitylabelsall models 8hlz, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hlz is a 6 chain structure with sequence from Monkeypox virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5IXP2_MONPV Publication Abstract from PubMed The ongoing global pandemic caused by a variant of the monkeypox (or mpox) virus (MPXV) has prompted widespread concern. The MPXV DNA polymerase holoenzyme, consisting of F8, A22, and E4, is vital for replicating the viral genome and represents a crucial target for the development of antiviral drugs. However, the assembly and working mechanism for the DNA polymerase holoenzyme of MPXV remains elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the DNA polymerase holoenzyme at an overall resolution of 3.5 A. Unexpectedly, the holoenzyme is assembled as a dimer of heterotrimers, of which the extra interface between the thumb domain of F8 and A22 shows a clash between A22 and substrate DNA, suggesting an autoinhibition state. Addition of exogenous double-stranded DNA shifts the hexamer into trimer exposing DNA binding sites, potentially representing a more active state. Our findings provide crucial steps toward developing targeted antiviral therapies for MPXV and related viruses. Structural basis for the assembly of the DNA polymerase holoenzyme from a monkeypox virus variant.,Li Y, Shen Y, Hu Z, Yan R Sci Adv. 2023 Apr 21;9(16):eadg2331. doi: 10.1126/sciadv.adg2331. Epub 2023 Apr , 19. PMID:37075110 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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