A detailed view of a ribosomal active site: The structure of the L11- RNA complex

Brian T. Wimberly; Rebecca Guymon; John P. McCutcheon; Stephen W. White; V. Ramakrishnan

doi:10.1016/S0092-8674(00)80759-X

A detailed view of a ribosomal active site: The structure of the L11- RNA complex

Brian T. Wimberly, Rebecca Guymon, John P. McCutcheon, Stephen W. White, V. Ramakrishnan

Research output: Contribution to journal › Article › peer-review

299 Scopus citations

Abstract

We report the crystal structure of a 58 nucleotide fragment of 23S ribosomal RNA bound to ribosomal protein L11. This highly conserved ribonucleoprotein domain is the target for the thiostrepton family of antibiotics that disrupt elongation factor function. The highly compact RNA has both familiar and novel structural motifs. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA. The sites of mutations conferring resistance to thiostrepton and micrococcin line a narrow cleft between the RNA and the N- terminal domain. These antibiotics are proposed to bind in this cleft, locking the putative switch and interfering with the function of elongation factors.

Original language	English (US)
Pages (from-to)	491-502
Number of pages	12
Journal	Cell
Volume	97
Issue number	4
DOIs	https://doi.org/10.1016/S0092-8674(00)80759-X
State	Published - May 14 1999
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/S0092-8674(00)80759-X

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title = "A detailed view of a ribosomal active site: The structure of the L11- RNA complex",

abstract = "We report the crystal structure of a 58 nucleotide fragment of 23S ribosomal RNA bound to ribosomal protein L11. This highly conserved ribonucleoprotein domain is the target for the thiostrepton family of antibiotics that disrupt elongation factor function. The highly compact RNA has both familiar and novel structural motifs. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA. The sites of mutations conferring resistance to thiostrepton and micrococcin line a narrow cleft between the RNA and the N- terminal domain. These antibiotics are proposed to bind in this cleft, locking the putative switch and interfering with the function of elongation factors.",

author = "Wimberly, {Brian T.} and Rebecca Guymon and McCutcheon, {John P.} and White, {Stephen W.} and V. Ramakrishnan",

note = "Funding Information: We thank R. M. Sweet and S. Sclafani for help with data collection on beamline X12C at the NSLS at Brookhaven National Laboratory; S. E. Gerchman for constructing the clone of L11 used in this study; Sandra Searles for the RNA transcription vectors pSS419 and pSS437; T. Terwilliger for advice with phasing using SOLVE; E. de la Fortelle for advice with phasing using SHARP; and J. P. Abrahams for advice with the use of input solvent masks in SOLOMON. This work was supported by NIH grant GM 44973 (S. W. W. and V. R.). S. W. W. also acknowledges the continued support of the American Lebanese Syrian Associated Charities (ALSAC).",

year = "1999",

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doi = "10.1016/S0092-8674(00)80759-X",

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T1 - A detailed view of a ribosomal active site

T2 - The structure of the L11- RNA complex

AU - Wimberly, Brian T.

AU - Guymon, Rebecca

AU - McCutcheon, John P.

AU - White, Stephen W.

AU - Ramakrishnan, V.

N1 - Funding Information: We thank R. M. Sweet and S. Sclafani for help with data collection on beamline X12C at the NSLS at Brookhaven National Laboratory; S. E. Gerchman for constructing the clone of L11 used in this study; Sandra Searles for the RNA transcription vectors pSS419 and pSS437; T. Terwilliger for advice with phasing using SOLVE; E. de la Fortelle for advice with phasing using SHARP; and J. P. Abrahams for advice with the use of input solvent masks in SOLOMON. This work was supported by NIH grant GM 44973 (S. W. W. and V. R.). S. W. W. also acknowledges the continued support of the American Lebanese Syrian Associated Charities (ALSAC).

PY - 1999/5/14

Y1 - 1999/5/14

N2 - We report the crystal structure of a 58 nucleotide fragment of 23S ribosomal RNA bound to ribosomal protein L11. This highly conserved ribonucleoprotein domain is the target for the thiostrepton family of antibiotics that disrupt elongation factor function. The highly compact RNA has both familiar and novel structural motifs. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA. The sites of mutations conferring resistance to thiostrepton and micrococcin line a narrow cleft between the RNA and the N- terminal domain. These antibiotics are proposed to bind in this cleft, locking the putative switch and interfering with the function of elongation factors.

AB - We report the crystal structure of a 58 nucleotide fragment of 23S ribosomal RNA bound to ribosomal protein L11. This highly conserved ribonucleoprotein domain is the target for the thiostrepton family of antibiotics that disrupt elongation factor function. The highly compact RNA has both familiar and novel structural motifs. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA. The sites of mutations conferring resistance to thiostrepton and micrococcin line a narrow cleft between the RNA and the N- terminal domain. These antibiotics are proposed to bind in this cleft, locking the putative switch and interfering with the function of elongation factors.

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SP - 491

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JO - Cell

JF - Cell

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A detailed view of a ribosomal active site: The structure of the L11- RNA complex

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