Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot
SARS-CoV-2 produces two long viral protein precursors from one open reading frame using a highly conserved RNA pseudoknot that enhances programmed -1 ribosomal frameshifting. The 1.3 Å-resolution X-ray structure of the pseudoknot reveals three coaxially stacked helices buttressed by idiosyncratic ba...
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Veröffentlicht in: | RNA (Cambridge) 2022-02, Vol.28 (2), p.239-249 |
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creator | Jones, Christopher P Ferré-D'Amaré, Adrian R |
description | SARS-CoV-2 produces two long viral protein precursors from one open reading frame using a highly conserved RNA pseudoknot that enhances programmed -1 ribosomal frameshifting. The 1.3 Å-resolution X-ray structure of the pseudoknot reveals three coaxially stacked helices buttressed by idiosyncratic base triples from loop residues. This structure represents a frameshift-stimulating state that must be deformed by the ribosome and exhibits base-triple-adjacent pockets that could be targeted by future small-molecule therapeutics. |
doi_str_mv | 10.1261/rna.078825.121 |
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The 1.3 Å-resolution X-ray structure of the pseudoknot reveals three coaxially stacked helices buttressed by idiosyncratic base triples from loop residues. This structure represents a frameshift-stimulating state that must be deformed by the ribosome and exhibits base-triple-adjacent pockets that could be targeted by future small-molecule therapeutics.</description><identifier>ISSN: 1355-8382</identifier><identifier>EISSN: 1469-9001</identifier><identifier>DOI: 10.1261/rna.078825.121</identifier><identifier>PMID: 34845084</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Codon, Terminator ; Coronaviruses ; Crystal structure ; Crystallography, X-Ray ; Frameshifting, Ribosomal ; Models, Molecular ; Mutation ; Nucleic Acid Conformation ; RNA, Viral - chemistry ; RNA, Viral - genetics ; SARS-CoV-2 - genetics ; Severe acute respiratory syndrome coronavirus 2</subject><ispartof>RNA (Cambridge), 2022-02, Vol.28 (2), p.239-249</ispartof><rights>Published by Cold Spring Harbor Laboratory Press for the RNA Society.</rights><rights>Copyright Cold Spring Harbor Laboratory Press Feb 2022</rights><rights>2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-144329680f71a96e2092e7dcdaf4847b273f4cdc4b8af0c0cb186bc7e2d255083</citedby><cites>FETCH-LOGICAL-c418t-144329680f71a96e2092e7dcdaf4847b273f4cdc4b8af0c0cb186bc7e2d255083</cites><orcidid>0000-0001-7780-5278 ; 0000-0003-4549-1619</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906546/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906546/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34845084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jones, Christopher P</creatorcontrib><creatorcontrib>Ferré-D'Amaré, Adrian R</creatorcontrib><title>Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot</title><title>RNA (Cambridge)</title><addtitle>RNA</addtitle><description>SARS-CoV-2 produces two long viral protein precursors from one open reading frame using a highly conserved RNA pseudoknot that enhances programmed -1 ribosomal frameshifting. The 1.3 Å-resolution X-ray structure of the pseudoknot reveals three coaxially stacked helices buttressed by idiosyncratic base triples from loop residues. This structure represents a frameshift-stimulating state that must be deformed by the ribosome and exhibits base-triple-adjacent pockets that could be targeted by future small-molecule therapeutics.</description><subject>Codon, Terminator</subject><subject>Coronaviruses</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Frameshifting, Ribosomal</subject><subject>Models, Molecular</subject><subject>Mutation</subject><subject>Nucleic Acid Conformation</subject><subject>RNA, Viral - chemistry</subject><subject>RNA, Viral - genetics</subject><subject>SARS-CoV-2 - genetics</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><issn>1355-8382</issn><issn>1469-9001</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1rFTEUxYMotla3LiXgpi7mma_JZDZCeagtFAqtug2ZzE3f1JnkmY8H77835dViu0rOvb97uJeD0HtKVpRJ-jl6syKdUqytmr5Ax1TIvukJoS_rn7dto7hiR-hNSne1yGv7NTriQomWKHGM_DruUzYzTjkWm0sEHBzOG8AJdlCVsSUDjpC2UzQ5xD1Oez_GsAC2IQZvdlMsCTN8enN2fdOsw6-GfcIumgXSZnJ58rd4m6CM4bcP-S165cyc4N3De4J-fvv6Y33eXF59v1ifXTZWUJUbKgRnvVTEddT0EhjpGXSjHY2rm3cD67gTdrRiUMYRS-xAlRxsB2xkbT2Mn6AvB99tGRYYLfgczay3cVpM3OtgJv2046eNvg07rXoiWyGrwemDQQx_CqSslylZmGfjIZSkmSRCcdFJVtGPz9C7UGou8z3FOiUJVW2lVgfKxpBSBPe4DCX6PkpdR_QhyqppHfjw_wmP-L_s-F8uL5vW</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Jones, Christopher P</creator><creator>Ferré-D'Amaré, Adrian R</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7780-5278</orcidid><orcidid>https://orcid.org/0000-0003-4549-1619</orcidid></search><sort><creationdate>202202</creationdate><title>Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot</title><author>Jones, Christopher P ; Ferré-D'Amaré, Adrian R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-144329680f71a96e2092e7dcdaf4847b273f4cdc4b8af0c0cb186bc7e2d255083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Codon, Terminator</topic><topic>Coronaviruses</topic><topic>Crystal structure</topic><topic>Crystallography, X-Ray</topic><topic>Frameshifting, Ribosomal</topic><topic>Models, Molecular</topic><topic>Mutation</topic><topic>Nucleic Acid Conformation</topic><topic>RNA, Viral - chemistry</topic><topic>RNA, Viral - genetics</topic><topic>SARS-CoV-2 - genetics</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jones, Christopher P</creatorcontrib><creatorcontrib>Ferré-D'Amaré, Adrian R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RNA (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, Christopher P</au><au>Ferré-D'Amaré, Adrian R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot</atitle><jtitle>RNA (Cambridge)</jtitle><addtitle>RNA</addtitle><date>2022-02</date><risdate>2022</risdate><volume>28</volume><issue>2</issue><spage>239</spage><epage>249</epage><pages>239-249</pages><issn>1355-8382</issn><eissn>1469-9001</eissn><abstract>SARS-CoV-2 produces two long viral protein precursors from one open reading frame using a highly conserved RNA pseudoknot that enhances programmed -1 ribosomal frameshifting. The 1.3 Å-resolution X-ray structure of the pseudoknot reveals three coaxially stacked helices buttressed by idiosyncratic base triples from loop residues. This structure represents a frameshift-stimulating state that must be deformed by the ribosome and exhibits base-triple-adjacent pockets that could be targeted by future small-molecule therapeutics.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>34845084</pmid><doi>10.1261/rna.078825.121</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7780-5278</orcidid><orcidid>https://orcid.org/0000-0003-4549-1619</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Codon, Terminator Coronaviruses Crystal structure Crystallography, X-Ray Frameshifting, Ribosomal Models, Molecular Mutation Nucleic Acid Conformation RNA, Viral - chemistry RNA, Viral - genetics SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 |
title | Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot |
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