Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000775125> ?p ?o ?g. }
- W2000775125 endingPage "24" @default.
- W2000775125 startingPage "14" @default.
- W2000775125 abstract "The hepatitis C virus (HCV) replicates its genome in replication complexes located in micro-vesicles derived from endoplasmic reticulum. The composition of these replication complexes indicates that proteins, both viral and cellular in origin, are at high concentrations. Under these conditions, protein-protein interactions must occur although their role in the replication pathways is unknown. HCV RNA-dependent RNA-polymerase (NS5B) initiates RNA synthesis in these vesicles by a de novo (DN) mechanism. After initiation, newly synthesized dsRNA could induce conformational changes that direct the transition from an initiating complex into a processive elongation complex. In this report, we analyze the role played by NS5B-NS5B intermolecular interactions controlling these conformational rearrangements. Based on NS5B protein-protein docking and molecular dynamics simulations, we constructed mutants of residues predicted to be involved in protein-protein interactions. Changes at these positions induced severe defects in both the activity of the enzyme and the replication of a subgenomic replicon. Thus, mutations at the interaction surface decreased both DN synthesis initiation and processive elongation activities. Based on this analysis, we define at an atomic level an NS5B homomeric interaction model that connects the T-helix in the thumb subdomain of one monomer, with the F-helix of the fingers subdomain in other monomer. Knowing the molecular determinants involved in viral replication could be helpful to delineate new and powerful antiviral strategies." @default.
- W2000775125 created "2016-06-24" @default.
- W2000775125 creator A5000965333 @default.
- W2000775125 creator A5007883362 @default.
- W2000775125 creator A5013669317 @default.
- W2000775125 creator A5025012665 @default.
- W2000775125 creator A5025230655 @default.
- W2000775125 creator A5044389148 @default.
- W2000775125 creator A5053951636 @default.
- W2000775125 creator A5058336143 @default.
- W2000775125 creator A5086345240 @default.
- W2000775125 date "2014-08-01" @default.
- W2000775125 modified "2023-10-18" @default.
- W2000775125 title "Hepatitis C virus polymerase–polymerase contact interface: Significance for virus replication and antiviral design" @default.
- W2000775125 cites W1531200550 @default.
- W2000775125 cites W1781471159 @default.
- W2000775125 cites W1932632320 @default.
- W2000775125 cites W1965362916 @default.
- W2000775125 cites W1965962980 @default.
- W2000775125 cites W1972459659 @default.
- W2000775125 cites W1973711348 @default.
- W2000775125 cites W1980208379 @default.
- W2000775125 cites W1992048113 @default.
- W2000775125 cites W1995000176 @default.
- W2000775125 cites W1995520533 @default.
- W2000775125 cites W1997131757 @default.
- W2000775125 cites W2007372000 @default.
- W2000775125 cites W2008304259 @default.
- W2000775125 cites W2010546204 @default.
- W2000775125 cites W2021416489 @default.
- W2000775125 cites W2022618835 @default.
- W2000775125 cites W2023490488 @default.
- W2000775125 cites W2027166401 @default.
- W2000775125 cites W2030140637 @default.
- W2000775125 cites W2031926002 @default.
- W2000775125 cites W2036894316 @default.
- W2000775125 cites W2049867962 @default.
- W2000775125 cites W2052717087 @default.
- W2000775125 cites W2054358831 @default.
- W2000775125 cites W2054788798 @default.
- W2000775125 cites W2054896136 @default.
- W2000775125 cites W2060781852 @default.
- W2000775125 cites W2063328126 @default.
- W2000775125 cites W2067108917 @default.
- W2000775125 cites W2067371216 @default.
- W2000775125 cites W2075860587 @default.
- W2000775125 cites W2092333889 @default.
- W2000775125 cites W2092558702 @default.
- W2000775125 cites W2093194919 @default.
- W2000775125 cites W2097857791 @default.
- W2000775125 cites W2102030104 @default.
- W2000775125 cites W2102312699 @default.
- W2000775125 cites W2103090903 @default.
- W2000775125 cites W2103325328 @default.
- W2000775125 cites W2106870343 @default.
- W2000775125 cites W2110670926 @default.
- W2000775125 cites W2110734032 @default.
- W2000775125 cites W2110869427 @default.
- W2000775125 cites W2112743424 @default.
- W2000775125 cites W2117717845 @default.
- W2000775125 cites W2118413931 @default.
- W2000775125 cites W2127508149 @default.
- W2000775125 cites W2129583806 @default.
- W2000775125 cites W2130479394 @default.
- W2000775125 cites W2132069032 @default.
- W2000775125 cites W2132537530 @default.
- W2000775125 cites W2136729627 @default.
- W2000775125 cites W2144881432 @default.
- W2000775125 cites W2147290736 @default.
- W2000775125 cites W2149881416 @default.
- W2000775125 cites W2151898297 @default.
- W2000775125 cites W2154791057 @default.
- W2000775125 cites W2157281740 @default.
- W2000775125 cites W2163090431 @default.
- W2000775125 cites W2166528216 @default.
- W2000775125 cites W2170421654 @default.
- W2000775125 cites W2171249995 @default.
- W2000775125 cites W2289442398 @default.
- W2000775125 doi "https://doi.org/10.1016/j.antiviral.2014.04.009" @default.
- W2000775125 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24815023" @default.
- W2000775125 hasPublicationYear "2014" @default.
- W2000775125 type Work @default.
- W2000775125 sameAs 2000775125 @default.
- W2000775125 citedByCount "10" @default.
- W2000775125 countsByYear W20007751252016 @default.
- W2000775125 countsByYear W20007751252019 @default.
- W2000775125 countsByYear W20007751252020 @default.
- W2000775125 countsByYear W20007751252021 @default.
- W2000775125 countsByYear W20007751252022 @default.
- W2000775125 countsByYear W20007751252023 @default.
- W2000775125 crossrefType "journal-article" @default.
- W2000775125 hasAuthorship W2000775125A5000965333 @default.
- W2000775125 hasAuthorship W2000775125A5007883362 @default.
- W2000775125 hasAuthorship W2000775125A5013669317 @default.
- W2000775125 hasAuthorship W2000775125A5025012665 @default.
- W2000775125 hasAuthorship W2000775125A5025230655 @default.
- W2000775125 hasAuthorship W2000775125A5044389148 @default.
- W2000775125 hasAuthorship W2000775125A5053951636 @default.