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Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
2018 (English)In: Annual Review of Biophysics, ISSN 1936-122X, E-ISSN 1936-1238, p. 525-548Article, review/survey (Refereed) Published
Abstract [en]

Accurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex (T-3) with elongation factor Tu (EF-Tu) and guanosine-5'-triphosphate (GTP). We define actual accuracy (A(I)(nc)) of a particular protein synthesis system as its current accuracy and the effective selectivity (d(eI)(nc)) as A(I)(nc) in the limit of zero ribosomal binding affinity for T-3. Intrinsic selectivity (D-I(nc)), defined as the upper thermodynamic limit of d(eI)(nc), is determined by the free energy difference between near-cognate and cognate T-3 in the pre-GTP hydrolysis state on the ribosome. D-I(nc) is much larger than d(eI)(nc), suggesting the possibility of a considerable increase in d(eI)(nc) and A(I)(nc) at negligible kinetic cost. Induced fit increases A(I)(nc) and d(eI)(nc) without affecting D-I(nc), and aminoglycoside antibiotics reduce A(I)(nc) and d(eI)(nc) at unaltered D-I(nc).

Place, publisher, year, edition, pages
2018. p. 525-548
Keywords [en]
induced fit, ribosome, translation accuracy, initial selection, tautomers
National Category
Biophysics
Identifiers
URN: urn:nbn:se:uu:diva-361439DOI: 10.1146/annurev-biophys-060414-034148ISI: 000433056800024PubMedID: 29792818ISBN: 978-0-8243-1847-5 (print)OAI: oai:DiVA.org:uu-361439DiVA, id: diva2:1269378
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved

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Pavlov, MichaelEhrenberg, Måns

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