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-Structure paper
タイトル | Structural basis for the assembly of the DNA polymerase holoenzyme from a monkeypox virus variant. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 16, Page eadg2331, Year 2023 |
掲載日 | 2023年4月21日 |
著者 | Yaning Li / Yaping Shen / Ziwei Hu / Renhong Yan / |
PubMed 要旨 | 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 ...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 Å. 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. |
リンク | Sci Adv / PubMed:37075110 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 3.5 Å |
構造データ | EMDB-34885: F8-A22-E4 complex in hexameric form local map EMDB-34886, PDB-8hlz: EMDB-34887, PDB-8hm0: |
由来 |
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キーワード | REPLICATION / MPXV / complex / RECOMBINATION |