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-Structure paper
タイトル | Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome. |
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ジャーナル・号・ページ | Science, Vol. 372, Issue 6548, Page 1306-1313, Year 2021 |
掲載日 | 2021年6月18日 |
著者 | Pramod R Bhatt / Alain Scaiola / Gary Loughran / Marc Leibundgut / Annika Kratzel / Romane Meurs / René Dreos / Kate M O'Connor / Angus McMillan / Jeffrey W Bode / Volker Thiel / David Gatfield / John F Atkins / Nenad Ban / |
PubMed 要旨 | Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent ...Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent RNA polymerase and downstream proteins. Here, we present the cryo-electron microscopy structure of a translating mammalian ribosome primed for frameshifting on the viral RNA. The viral RNA adopts a pseudoknot structure that lodges at the entry to the ribosomal messenger RNA (mRNA) channel to generate tension in the mRNA and promote frameshifting, whereas the nascent viral polyprotein forms distinct interactions with the ribosomal tunnel. Biochemical experiments validate the structural observations and reveal mechanistic and regulatory features that influence frameshifting efficiency. Finally, we compare compounds previously shown to reduce frameshifting with respect to their ability to inhibit SARS-CoV-2 replication, establishing coronavirus frameshifting as a target for antiviral intervention. |
リンク | Science / PubMed:34029205 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.2 - 6.0 Å |
構造データ | EMDB-12756, PDB-7o7y: EMDB-12757, PDB-7o7z: EMDB-12758, PDB-7o80: EMDB-12759, PDB-7o81: EMDB-12760: |
化合物 | ChemComp-SPD: ChemComp-SPM: ChemComp-MG: ChemComp-UNX: ChemComp-ZN: ChemComp-HOH: ChemComp-GTP: ChemComp-SF4: |
由来 |
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キーワード | RIBOSOME / Frameshift / virus / pseudoknot |