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  EF-G-dependent GTPase on the ribosome: Conformational change and fusidic acid inhibition

Seo, H.-S., Abedin, S., Kamp, D., Wilson, D. N., Nierhaus, K., & Cooperman, B. S. (2006). EF-G-dependent GTPase on the ribosome: Conformational change and fusidic acid inhibition. Biochemistry, 45(8), 2504-2514. doi:10.1021/bi0516677.

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Seo, Hyuk-Soo, Author
Abedin, Sameem, Author
Kamp, Detlev1, Author
Wilson, Daniel N.2, Author              
Nierhaus, Knud3, Author              
Cooperman, Barry S., Author
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
3Ribosomes, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433558              

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 Abstract: Protein synthesis studies increasingly focus on delineating the nature of conformational changes occurring as the ribosome exerts its catalytic functions. Here, we use FRET to examine such changes during single-turnover EF-G-dependent GTPase on vacant ribosomes and to elucidate the mechanism by which fusidic acid (FA) inhibits multiple-turnover EF-G·GTPase. Our measurements focus on the distance between the G' region of EF-G and the N-terminal region of L11 (L11-NTD), located within the GTPase activation center of the ribosome. We demonstrate that single-turnover ribosome-dependent EF-G GTPase proceeds according to a kinetic scheme in which rapid G' to L11-NTD movement requires prior GTP hydrolysis and, via branching pathways, either precedes Pi release (major pathway) or occurs simultaneously with it (minor pathway). Such movement retards Pi release, with the result that Pi release is essentially rate-determining in single-turnover GTPase. This is the most significant difference between the EF-G·GTPase activities of vacant and translocating ribosomes [Savelsbergh, A., Katunin, V. I., Mohr, D., Peske, F., Rodnina, M. V., and Wintermeyer, W. (2003) Mol. Cell 11, 1517-1523], which are otherwise quite similar. Both the G' to L11-NTD movement and Pi release are strongly inhibited by thiostrepton but not by FA. Contrary to the standard view that FA permits only a single round of GTP hydrolysis [Bodley, J. W., Zieve, F. J., and Lin, L. (1970) J. Biol. Chem. 245, 5662-5667], we find that FA functions rather as a slow inhibitor of EF-G·GTPase, permitting a number of GTPase turnovers prior to complete inhibition while inducing a closer approach of EF-G to the GAC than is seen during normal turnover.

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Language(s): eng - English
 Dates: 2006-02-01
 Publication Status: Published in print
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 Identifiers: eDoc: 305598
DOI: 10.1021/bi0516677
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Title: Biochemistry
Source Genre: Journal
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Pages: - Volume / Issue: 45 (8) Sequence Number: - Start / End Page: 2504 - 2514 Identifier: ISSN: 0006-2960