FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2932873695> ?p ?o ?g. }

• W2932873695 endingPage "8100" @default.
• W2932873695 startingPage "8088" @default.
• W2932873695 abstract "The L protein of arena- and bunyaviruses is structurally and functionally related to the orthomyxovirus polymerase complex. It plays a central role in the viral life cycle, as it replicates the virus genome and generates viral mRNA via a cap-snatching mechanism. Here, we aimed to biochemically characterize the L protein of Lassa virus, a human-pathogenic arenavirus endemic in West Africa. Full-length 250-kDa L protein was expressed using a baculovirus expression system. A low-resolution structure calculated from small-angle X-ray scattering data revealed a conformation similar to that in the crystal structure of the orthomyxovirus polymerase complex. Although the L protein did not exhibit cap-snatching endonuclease activity, it synthesized RNA in vitro. RNA polymerization required manganese rather than magnesium ions, was independent of nucleotide primers, and was inhibited by viral Z protein. Maximum activity was mediated by double-stranded promoter sequences with a minimum length of 17 nucleotides, containing a nontemplated 5′-G overhang, as in the natural genome context, as well as the naturally occurring base mismatches between the complementary promoter strands. Experiments with various short primers revealed the presence of two replication initiation sites at the template strand and evidence for primer translocation as proposed by the prime-and-realign hypothesis. Overall, our findings provide the foundation for a detailed understanding of the mechanistic differences and communalities in the polymerase proteins of segmented negative-strand RNA viruses and for the search for antiviral compounds targeting the RNA polymerase of Lassa virus. The L protein of arena- and bunyaviruses is structurally and functionally related to the orthomyxovirus polymerase complex. It plays a central role in the viral life cycle, as it replicates the virus genome and generates viral mRNA via a cap-snatching mechanism. Here, we aimed to biochemically characterize the L protein of Lassa virus, a human-pathogenic arenavirus endemic in West Africa. Full-length 250-kDa L protein was expressed using a baculovirus expression system. A low-resolution structure calculated from small-angle X-ray scattering data revealed a conformation similar to that in the crystal structure of the orthomyxovirus polymerase complex. Although the L protein did not exhibit cap-snatching endonuclease activity, it synthesized RNA in vitro. RNA polymerization required manganese rather than magnesium ions, was independent of nucleotide primers, and was inhibited by viral Z protein. Maximum activity was mediated by double-stranded promoter sequences with a minimum length of 17 nucleotides, containing a nontemplated 5′-G overhang, as in the natural genome context, as well as the naturally occurring base mismatches between the complementary promoter strands. Experiments with various short primers revealed the presence of two replication initiation sites at the template strand and evidence for primer translocation as proposed by the prime-and-realign hypothesis. Overall, our findings provide the foundation for a detailed understanding of the mechanistic differences and communalities in the polymerase proteins of segmented negative-strand RNA viruses and for the search for antiviral compounds targeting the RNA polymerase of Lassa virus." @default.
• W2932873695 created "2019-04-11" @default.
• W2932873695 creator A5023412513 @default.
• W2932873695 creator A5041242389 @default.
• W2932873695 creator A5051191695 @default.
• W2932873695 creator A5062254965 @default.
• W2932873695 creator A5062723541 @default.
• W2932873695 date "2019-05-01" @default.
• W2932873695 modified "2023-10-10" @default.
• W2932873695 title "Biochemical characterization of the Lassa virus L protein" @default.
• W2932873695 cites W1501087466 @default.
• W2932873695 cites W1677665692 @default.
• W2932873695 cites W1689624428 @default.
• W2932873695 cites W1738480851 @default.
• W2932873695 cites W1857763546 @default.
• W2932873695 cites W1977038370 @default.
• W2932873695 cites W1981040371 @default.
• W2932873695 cites W1982126789 @default.
• W2932873695 cites W1986838723 @default.
• W2932873695 cites W1987065874 @default.
• W2932873695 cites W1992077786 @default.
• W2932873695 cites W1997862281 @default.
• W2932873695 cites W1999586024 @default.
• W2932873695 cites W2012058790 @default.
• W2932873695 cites W2013980053 @default.
• W2932873695 cites W2026920658 @default.
• W2932873695 cites W2027847351 @default.
• W2932873695 cites W2034998644 @default.
• W2932873695 cites W2044600321 @default.
• W2932873695 cites W2050091361 @default.
• W2932873695 cites W2053153901 @default.
• W2932873695 cites W2057563780 @default.
• W2932873695 cites W2079236927 @default.
• W2932873695 cites W2087818806 @default.
• W2932873695 cites W2096003342 @default.
• W2932873695 cites W2097857791 @default.
• W2932873695 cites W2097899002 @default.
• W2932873695 cites W2098475932 @default.
• W2932873695 cites W2099540110 @default.
• W2932873695 cites W2100243425 @default.
• W2932873695 cites W2103747393 @default.
• W2932873695 cites W2113451459 @default.
• W2932873695 cites W2118409273 @default.
• W2932873695 cites W2124983865 @default.
• W2932873695 cites W2125282138 @default.
• W2932873695 cites W2126635382 @default.
• W2932873695 cites W2132629607 @default.
• W2932873695 cites W2140974872 @default.
• W2932873695 cites W2144881432 @default.
• W2932873695 cites W2145258477 @default.
• W2932873695 cites W2146298240 @default.
• W2932873695 cites W2147343114 @default.
• W2932873695 cites W2149885731 @default.
• W2932873695 cites W2150576297 @default.
• W2932873695 cites W2155952708 @default.
• W2932873695 cites W2164361934 @default.
• W2932873695 cites W2172007859 @default.
• W2932873695 cites W2238439239 @default.
• W2932873695 cites W2272563378 @default.
• W2932873695 cites W2276744781 @default.
• W2932873695 cites W2426189081 @default.
• W2932873695 cites W2437090616 @default.
• W2932873695 cites W2580330110 @default.
• W2932873695 cites W2606124384 @default.
• W2932873695 cites W2615593829 @default.
• W2932873695 cites W2707646777 @default.
• W2932873695 cites W2766233058 @default.
• W2932873695 cites W2800248815 @default.
• W2932873695 cites W4240574896 @default.
• W2932873695 doi "https://doi.org/10.1074/jbc.ra118.006973" @default.
• W2932873695 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6527160" @default.
• W2932873695 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30926610" @default.
• W2932873695 hasPublicationYear "2019" @default.
• W2932873695 type Work @default.
• W2932873695 sameAs 2932873695 @default.
• W2932873695 citedByCount "30" @default.
• W2932873695 countsByYear W29328736952019 @default.
• W2932873695 countsByYear W29328736952020 @default.
• W2932873695 countsByYear W29328736952021 @default.
• W2932873695 countsByYear W29328736952022 @default.
• W2932873695 countsByYear W29328736952023 @default.
• W2932873695 crossrefType "journal-article" @default.
• W2932873695 hasAuthorship W2932873695A5023412513 @default.
• W2932873695 hasAuthorship W2932873695A5041242389 @default.
• W2932873695 hasAuthorship W2932873695A5051191695 @default.
• W2932873695 hasAuthorship W2932873695A5062254965 @default.
• W2932873695 hasAuthorship W2932873695A5062723541 @default.
• W2932873695 hasBestOaLocation W29328736951 @default.
• W2932873695 hasConcept C104317684 @default.
• W2932873695 hasConcept C10852380 @default.
• W2932873695 hasConcept C140704245 @default.
• W2932873695 hasConcept C153911025 @default.
• W2932873695 hasConcept C154317977 @default.
• W2932873695 hasConcept C159047783 @default.
• W2932873695 hasConcept C178790620 @default.
• W2932873695 hasConcept C185592680 @default.
• W2932873695 hasConcept C202751555 @default.
• W2932873695 hasConcept C2522874641 @default.

• next