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-Structure paper
タイトル | Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 7018, Year 2021 |
掲載日 | 2021年12月2日 |
著者 | Tomas Kouba / Dominik Vogel / Sigurdur R Thorkelsson / Emmanuelle R J Quemin / Harry M Williams / Morlin Milewski / Carola Busch / Stephan Günther / Kay Grünewald / Maria Rosenthal / Stephen Cusack / |
PubMed 要旨 | Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we ...Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we present nine cryo-EM structures of the L protein in the apo-, promoter-bound pre-initiation and active RNA synthesis states. We characterize distinct binding pockets for the conserved 3' and 5' promoter RNAs and show how full-promoter binding induces a distinct pre-initiation conformation. In the apo- and early elongation states, the endonuclease is inhibited by two distinct L protein peptides, whereas in the pre-initiation state it is uninhibited. In the early elongation state, a template-product duplex is bound in the active site cavity together with an incoming non-hydrolysable nucleotide and the full C-terminal region of the L protein, including the putative cap-binding domain, is well-ordered. These data advance our mechanistic understanding of how this flexible and multifunctional molecular machine is activated. |
リンク | Nat Commun / PubMed:34857749 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.7 - 3.89 Å |
構造データ | EMDB-12807, PDB-7och: EMDB-12860, PDB-7oe3: EMDB-12861, PDB-7oe7: EMDB-12862, PDB-7oea: EMDB-12863, PDB-7oeb: EMDB-12953, PDB-7ojj: EMDB-12954, PDB-7ojk: EMDB-12955, PDB-7ojl: EMDB-12956, PDB-7ojn: |
化合物 | ChemComp-ZN: ChemComp-MG: ChemComp-HOH: ChemComp-MN: ChemComp-2KH: |
由来 |
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キーワード | VIRAL PROTEIN / Lassa virus RNA-dependent RNA polymerase viral RNA |