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-Structure paper
タイトル | Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 7166, Year 2021 |
掲載日 | 2021年12月9日 |
著者 | Chris H Hill / Lukas Pekarek / Sawsan Napthine / Anuja Kibe / Andrew E Firth / Stephen C Graham / Neva Caliskan / Ian Brierley / |
PubMed 要旨 | Programmed -1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we ...Programmed -1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we present the X-ray crystal structure of 2A and show that it selectively binds to a pseudoknot-like conformation of the PRF stimulatory RNA element in the viral genome. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, likely explaining the increase in PRF efficiency in the presence of 2A. Next, we demonstrate a strong interaction between 2A and the small ribosomal subunit and present a cryo-EM structure of 2A bound to initiated 70S ribosomes. Multiple copies of 2A bind to the 16S rRNA where they may compete for binding with initiation and elongation factors. Together, these results define the structural basis for RNA recognition by 2A, show how 2A-mediated stabilisation of an RNA pseudoknot promotes PRF, and reveal how 2A accumulation may shut down translation during virus infection. |
リンク | Nat Commun / PubMed:34887415 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.62 - 2.66 Å |
構造データ | EMDB-12635, PDB-7nwt: PDB-7bny: |
化合物 | ChemComp-SO4: ChemComp-HOH: ChemComp-MG: ChemComp-FME: ChemComp-ZN: |
由来 |
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キーワード | VIRAL PROTEIN / EMCV / cardiovirus / 2A / picornavirus / frameshifting / PRF / RNA-binding protein / protein-mediated frameshifting / ribosome-binding protein / beta-shell / RIBOSOME / 70S ribosome / initiation complex |