DOI: 10.1261/rna.2294806. Functional conformations of the L11–ribosomal RNA complex revealed by correlative analysis of cryo-EM and molecular dynamics simulations

Functional conformations of the L11–ribosomal RNA complex revealed by correlative analysis of cryo-EM and molecular dynamics simulations

10.1261/rna.2294806

Crossref journal-article

Cold Spring Harbor Laboratory

RNA (246)

Abstract

The interaction between the GTPase-associated center (GAC) and the aminoacyl-tRNA·EF-Tu·GTP ternary complex is of crucial importance in the dynamic process of decoding and tRNA accommodation. The GAC includes protein L11 and helices 43–44 of 23S rRNA (referred to as L11–rRNA complex). In this study, a method of fitting based on a systematic comparison between cryo-electron microscopy (cryo-EM) density maps and structures obtained by molecular dynamics simulations has been developed. This method has led to the finding of atomic models of the GAC that fit the EM maps with much improved cross-correlation coefficients compared with the fitting of the X-ray structure. Two types of conformations of the L11–rRNA complex, produced by the simulations, match the cryo-EM maps representing the states either bound or unbound to the aa-tRNA·EF-Tu·GTP ternary complex. In the bound state, the N-terminal domain of L11 is extended from its position in the crystal structure, and the base of nucleotide A1067 in the 23S ribosomal RNA is flipped out. This position of the base allows the RNA to reach the elbow region of the aminoacyl-tRNA when the latter is bound in the A/T site. In the unbound state, the N-terminal domain of L11 is rotated only slightly, and A1067 of the RNA is flipped back into the less-solvent-exposed position, as in the crystal structure. By matching our experimental cryo-EM maps with much improved cross-correlation coefficients compared to the crystal structure, these two conformations prove to be strong candidates of the two functional states.

Bibliography

Li, W., Sengupta, J., Rath, B. K., & Frank, J. (2006). Functional conformations of the L11âribosomal RNA complex revealed by correlative analysis of cryo-EM and molecular dynamics simulations. RNA, 12(7), 1240â1253.

Authors 4

Wen Li (first)
Jayati Sengupta (additional)
Bimal K. Rath (additional)
Joachim Frank (additional)

References 33 Referenced 39

10.1038/10695
10.1083/jcb.150.3.447
10.1006/jmbi.2001.4907
10.1016/j.cell.2005.03.023
{'key': '2021112105410244000_12.7.1240.5', 'first-page': '493', 'article-title': 'Ribbons', 'volume': '277', 'author': 'Carson', 'year': '1997', 'journal-title': 'Acta Crystallogr. B'} / Acta Crystallogr. B / Ribbons by Carson (1997)
10.1126/science.284.5417.1171
10.1021/ja00124a002 / J. Am. Chem. Soc. / A second generation force field for the simulation of proteins and nucleic acids by Cornell (1995)
10.1016/0300-9084(87)90213-6 / Biochimie / On the nature of antibiotic binding sites in ribosomes by Cundliffe (1987)
10.1093/nar/gkg382
10.1038/35018597
10.1006/jsbi.1996.0030
10.1063/1.445869
10.1038/nature02332
10.1093/emboj/20.15.4214
10.1038/334362a0
10.1126/science.1060612
10.1016/S0092-8674(02)01086-3
10.1063/1.470043
10.1016/j.jsb.2003.09.029
10.1529/biophysj.104.054916
10.1016/S0304-3991(02)00333-9
10.1093/nar/22.3.357
10.1073/pnas.0503456102
10.1126/science.1117230
Simmerling C. Elber R. Zhang J. (1995) in Modelling of biomolecular structure and mechanisms, Moil-View—A program for visualization of structure and dynamics of biomolecules and STO—A program for computing stochastic paths, in modeling of molecular structure and mechanisms, ed Pullman A. (Kluwer, Amsterdam), pp 241–265. (10.1007/978-94-011-0497-5_20)
10.1006/jmbi.1998.2387
{'key': '2021112105410244000_12.7.1240.27', 'first-page': '849', 'article-title': 'Ribosome interactions of aminoacyl-tRNA and elongation factor Tu in the codon-recognition complex', 'volume': '9', 'author': 'Stark', 'year': '2002', 'journal-title': 'Nat. Struct. Biol.'} / Nat. Struct. Biol. / Ribosome interactions of aminoacyl-tRNA and elongation factor Tu in the codon-recognition complex by Stark (2002)
10.1002/j.1460-2075.1994.tb06641.x / EMBO J. / A functional site of the GTPase-associated center within 28S ribosomal RNA probed with an anti-RNA autoantibody by Uchiumi (1994)
10.1093/emboj/cdf326
10.1038/nsb1003
10.1016/S0092-8674(03)00476-8
10.1080/00268977700102571
10.1016/S0092-8674(00)80759-X

Dates

Type	When
Created	19 years, 3 months ago (May 8, 2006, 9:40 p.m.)
Deposited	3 years, 9 months ago (Nov. 21, 2021, 8:46 a.m.)
Indexed	1 year, 5 months ago (March 4, 2024, 4:58 p.m.)
Issued	19 years, 3 months ago (May 8, 2006)
Published	19 years, 3 months ago (May 8, 2006)
Published Online	19 years, 3 months ago (May 8, 2006)
Published Print	19 years, 1 month ago (July 1, 2006)

Funders 0

None

BibTeX

@article{Li_2006, title={Functional conformations of the L11–ribosomal RNA complex revealed by correlative analysis of cryo-EM and molecular dynamics simulations}, volume={12}, ISSN={1469-9001}, url={http://dx.doi.org/10.1261/rna.2294806}, DOI={10.1261/rna.2294806}, number={7}, journal={RNA}, publisher={Cold Spring Harbor Laboratory}, author={Li, Wen and Sengupta, Jayati and Rath, Bimal K. and Frank, Joachim}, year={2006}, month=may, pages={1240–1253} }

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