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10.1021/acschembio.1c00324

http://scihub22266oqcxt.onion/10.1021/acschembio.1c00324
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suck abstract from ncbi


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pmid34328734      ACS+Chem+Biol 2021 ; 16 (8): 1469-1481
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  • The SARS-CoV-2 Programmed -1 Ribosomal Frameshifting Element Crystal Structure Solved to 2 09 A Using Chaperone-Assisted RNA Crystallography #MMPMID34328734
  • Roman C; Lewicka A; Koirala D; Li NS; Piccirilli JA
  • ACS Chem Biol 2021[Aug]; 16 (8): 1469-1481 PMID34328734show ga
  • The programmed -1 ribosomal frameshifting element (PFSE) of SARS-CoV-2 is a well conserved structured RNA found in all coronaviruses' genomes. By adopting a pseudoknot structure in the presence of the ribosome, the PFSE promotes a ribosomal frameshifting event near the stop codon of the first open reading frame Orf1a during translation of the polyprotein pp1a. Frameshifting results in continuation of pp1a via a new open reading frame, Orf1b, that produces the longer pp1ab polyprotein. Polyproteins pp1a and pp1ab produce nonstructural proteins NSPs 1-10 and NSPs 1-16, respectively, which contribute vital functions during the viral life cycle and must be present in the proper stoichiometry. Both drugs and sequence alterations that affect the stability of the -1 programmed ribosomal frameshifting element disrupt the stoichiometry of the NSPs produced, which compromise viral replication. For this reason, the -1 programmed frameshifting element is considered a promising drug target. Using chaperone assisted RNA crystallography, we successfully crystallized and solved the three-dimensional structure of the PFSE. We observe a three-stem H-type pseudoknot structure with the three stems stacked in a vertical orientation stabilized by two triple base pairs at the stem 1/stem 2 and stem 1/stem 3 junctions. This structure provides a new conformation of PFSE distinct from the bent conformations inferred from midresolution cryo-EM models and provides a high-resolution framework for mechanistic investigations and structure-based drug design.
  • |*Molecular Chaperones[MESH]
  • |Crystallography/*methods[MESH]
  • |Frameshifting, Ribosomal/*physiology[MESH]
  • |Humans[MESH]
  • |Models, Molecular[MESH]
  • |Nucleic Acid Conformation[MESH]
  • |RNA, Viral/genetics/*metabolism[MESH]
  • |Ribosomes/metabolism[MESH]
  • |SARS-CoV-2/genetics/*metabolism[MESH]
  • |Viral Proteins/chemistry/genetics/metabolism[MESH]


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