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- W2110035826 abstract "ribosomesin1981(2)immediatelyraisedthequestionof the importance of this site in addition to the established A- andP-sites. Thereafter, during almost 3 decades, the allosteric three-sitemodelwaselaborated,whichdefinesacross-talkbetweenthefirst(A)and the third site (E) in a sense of negative cooperativity during theribosomal elongation phase. It was based on the observation thatoccupation of the A-site after the decoding step releases the tRNAfrom E-site, and vice versa, occupation of the E-site induced a lowaffinity of the A-site (for review see Ref. 3). Evidence was presentedthatthelattereffectwasimportantfortheaccuracyofproteinsynthe-sis (4). We note that the allosteric three-site model is supported by awealth of data referenced in Refs. 3 and 4.Petropoulos and Green (1) reported that they failed to confirm theallostericthree-sitemodel.However,theydidnotpresentoneexper-iment addressing a possible negative cooperativity between A- andE-sites. Therefore the statement in the title is not supported by thepresented evidence. Rather in the first experiment they tested ourconclusionconcerninginitiation(unrelatedtoAandEallostery)thattheShine-DalgarnointeractioncanfunctionallyreplacethelackofanE-tRNA(4)anddemonstratedthatwemadeamistakeinthedesignofone mRNA, which might explain our results. Although we agree thatour conclusions using this mRNA no longer hold, we note that thesecond mRNA had no such error and showed a positive effect withnear-cognate tRNAs, leaving it still open as to whether the originalconclusion was right or wrong.The prediction of the allosteric three-site model that an occupiedE-site is beneficial for accuracy (3) could be fulfilled (4), whereasPetropoulosandGreenthoughttohaverejectedit(1).A-andpartic-ularly E-site occupancy can vary sharply depending on the ionicmilieu and the ribosome preparation and thus has to be carefullycontrolledaswealwaysdid,whereascorrespondingcontrolswerenotperformedinRef.1.Evenworse,insomeexperiments(Fig.2" @default.
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- W2110035826 date "2012-08-01" @default.
- W2110035826 modified "2023-09-30" @default.
- W2110035826 title "Problems with the Analyses of the Ribosomal Allosteric Three-site Model" @default.
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- W2110035826 doi "https://doi.org/10.1074/jbc.l112.381848" @default.
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