8i6h
Crystal structure of the African swine fever virus DNA sliding clamp (selenomethionine form)
Structural highlights
FunctionVF301_ASFB7 Plays a role in the inhibition of host innate immune system by acting as a negatively regulator of type I interferon production. Mechanistically, interacts with and prevents host IRF3 nuclear localization to inhibit its transcriptional activity.[1] Publication Abstract from PubMedAfrican swine fever virus (ASFV) is an important animal pathogen that is causing a current African swine fever pandemic and affecting pork industry globally. ASFV encodes at least 150 proteins, and the functions of many of them remain to be clarified. The ASFV protein E301R (pE301R) was predicted to be a DNA sliding clamp protein homolog working as a DNA replication processivity factor. However, structural evidence was lacking to support the existence of a ring-shaped sliding clamp in large eukaryotic DNA viruses. Here, we have solved a high-resolution crystal structure of pE301R and identified a canonical ring-shaped clamp comprising a pE301R trimer. Interestingly, this complete-toroidal structure is different from those of the monomeric clamp protein homolog, herpes simplex virus UL42, and the C-shaped dimeric human cytomegalovirus UL44, but highly homologous to that of the eukaryotic clamp homolog proliferating cell nuclear antigen. Moreover, pE301R has a unique N-terminal extension that is important in maintaining the trimeric form of the protein in solution, while specific features in length and surface electrostatic potential of its interdomain connector implies specificity in interactions with binding partners such as the viral DNA polymerase. Thus, our data pave the way for further dissection of the processivity clamp protein structural and functional diversity and ASFV DNA replication mechanisms. Crystal structure of African swine fever virus pE301R reveals a ring-shaped trimeric DNA sliding clamp.,Wu J, Zheng H, Gong P J Biol Chem. 2023 Jul;299(7):104872. doi: 10.1016/j.jbc.2023.104872. Epub 2023 , May 29. PMID:37257822[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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