Correlation between three-dimensional structure and chemical reactivity of transfer RNA

Robertus, Jon D.; Ladner, Jane E.; Finch, J. T.; Rhodes, Daniela; Brown, Raymond S.; Clark, Brian F. C.; Klug, A.

doi:10.1093/nar/1.7.927

Cited by 62 publications

(35 citation statements)

References 12 publications

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“…Our density map has led to an interpretation (1) in terms of a molecular model which accounts for most of the sequence invariances in the clover leaf formula and which is also in good agreement with the accessibility of the bases to chemical modification (10). The correlation coefficient (5) relating observed intensities to those calculated from our model is 57%.…”

Section: Discussionsupporting

confidence: 68%

“…2c, where however the full extent of the shrinkage is not depicted. It is noteworthy that the molecules can slide a distance of 10 At with respect to each other, before the anticodon loops in one column abut the CCA ends sandwiched between the anticodon stems in the next column. There is a similar translation in the region of z = '/2 so that the unit cell can shrink by about 20 A without any disturbance in molecular shape.…”

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confidence: 99%

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Conversation of the Molecular Structure of Yeast Phenylalanine Transfer RNA in Two Crystal Forms

Klug

Robertus

Ladner

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

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A comparison is made between the electron density maps of the monoclinic and orthorhombic crystal forms of yeast tRNAPhe which have been obtained respectively by ourselves and by another group. It is concluded that the molecular structures are essentially the same in both crystals, although the models derived from the maps are not the same. The relation between the two molecular packings is discussed, and it is suggested that the intermolecular contact in the orthorhombic form which is not present in the monoclinic form, may arise through base pairing of the anticodons of neighboring molecules.We have recently determined the crystal structure of a monoclinic form of yeast phenylalanine tRNA at 3-A resolution by x-ray crystallographic analysis (1), using the method of isomorphous replacement to obtain a map of the electron density in the crystal. The map is of sufficient quality to trace the ribose-phosphate chain over all the double helical regions of the familiar clover leaf formula and also over most of the loop sequences in between. As a result, we have been able to build a model which defines most of the various interactions involved in maintaining the tertiary structure. A model of the structure of the same molecule has also been proposed by a group at MIT who have obtained an electron density map of the orthorhombic crystal form to the same resolution (2). Although the crystal forms are different, there are common features in the unit-cell dimensions and symmetry and also in the distribution of x-ray intensities, so that the two structures are expected to be very similar (3). Our model has a similar overall shape to the MIT model, but our density maps differ in detail and our interpretations have major differences. Most of the nucleotide residues are differently placed in the two models and none of the tertiary interactions we have described are present in the MIT model.In a recent paper (4), the MIT workers have attempted to predict the density in the monoclinic crystal from the density map which they have obtained of the orthorhombic form. This procedure, though theoretically sound, can have many pitfalls in practice and may lead to questionable results at high resolution.Since a density map for the monoclinic crystal has now been obtained directly (1), it is possible to make a comparison of independent electron density maps for the two crystal structures. We do so in this paper. We conclude that the molecular configurations are virtually identical in the two crystal forms, but that there are errors in the MIT interpretation, not only in the loop regions, but also in the double * Present address: Department of Chemistry, The University of Texas, Austin, Texas. 3711 helical stem regions. The suggestion by the MIT group that the anticodon loop may have a slightly different conformation in the two structures is examined and seen to be wanting in evidence. We also discuss the relationship between the packing of the molecule in the two crystal forms. A suggestion is made on the nature of the new inter...

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Section: Discussionsupporting

confidence: 68%

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confidence: 99%

Conversation of the Molecular Structure of Yeast Phenylalanine Transfer RNA in Two Crystal Forms

Klug

Robertus

Ladner

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

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“…Several such studies have recently been made by physical techniques [9 -171. Chemical modification studies have proved to be an effective technique in the study of the static tertiary structure of tRNAs in solution [18]. In particular, sodium bisulphite has been widely used to convert accessible cytidine residues in tRNAs to uridine residues I19 -251.…”

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confidence: 99%

A Study of the Thermal Unfolding of Escherichia coli Phenylalanine Transfer RNA by Chemical Modification at Elevated Temperatures

Goddard

Lowdon

1978

European Journal of Biochemistry

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Escherichiu coli tRNAPh' was modified by 3 M sodium bisulphite pH 6.0 for 24 h in the temperature range 25 "C ( x 5 "C) to 55 "C and in the absence of added magnesium ions. The sites and extents of conversion of cytidines to uridine occurring at each temperature were determined by fingerprinting. The new sites of cytidine modification found at higher reaction temperatures were assumed to arise from breakage of secondary and tertiary structure hydrogen bonds involving cytidine residues. From these data, we conclude that hydrogen bonds within the 'complex core' of the tRNA (including the base pairs G-10 . C-25, C-1 1 G-24 and C-13 . G-21 within the dihydrouridine stem and the tertiary structure base pair G-15 . C-48 melt at a lower temperature than the tertiary structure hydrogen bonds between G-19 in the dihydrouridine loop and C-56 in the TYC loop.Conformational changes in tRNA have been postulated on aminoacylation [l -31 and on enzymatic binding of aminoacyl-tRNA to the ribosome-mRNA complex [4,5]. Certain tRNAs may exist in two different conformations, one active and one inactive in aminoacylation. It is therefore of interest to examine some of the conformations in which tRNA molecules may exist.The detailed X-ray crystallographic analysis of yeast tRNAPh ' [6,7] and accumulated primary sequence data [8] have vastly increased our understanding of the static conformation of tRNAs. However much remains unclear about the nature of the conformational changes which tRNAs could undergo in biochemical processes.The denaturation of tRNA is not a single cooperative process but a sequential one and its study provides a means of assessing the conformational stability of a tRNA. Several such studies have recently been made by physical techniques [9 -171. Chemical modification studies have proved to be an effective technique in the study of the static tertiary structure of tRNAs in solution [18]. In particular, sodium bisulphite has been widely used to convert accessible cytidine residues in tRNAs to uridine residues I19 -251. Here we report an extension of this technique, viz the analysis of E. coli tRNA;he modified with bisulphite at a series of elevated temperatures. We interpret our results in terms of the sequential unfolding of the tRNA and relate our interpretation to those of comparable physical studies. MATERIALS AND METHODS MaterialsSoluble 32P-labelled ribonucleic acid from E. coli K12 CA265 and all other radiochemicals were obtained from the Radiochemical Centre (Arnersham, Bucks). Mixed transfer RNA from E. coli K 12 CA265 was supplied by the Microbiological Research Establishment (Porton, Salisbury, Wilts.). Purified tRNAP'Ie (from E. coli MRE 600) and benzoylated DEAEcellulose were obtained from the Boehringer Corporation, poly(C) was from P-L Biochemicals.E. coli phenylalanyl-tRNA synthetase was prepared from E. coli MRE 600 cells, obtained from the Microbiological Research Establishment, by the method of Stulberg [26], the hydroxyapatite chromatography stages being omitted. Pancreatic ribonuclease, snake...

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“…Understanding how an RNA functions is directly connected to the understanding of its folding as well as interactions with other molecules [5,6,7,8]. In some cases, the well defined 3-D structures determined by X-ray diffraction provide great insight regarding the biological function and mechanisms [9,10,11,12]. However, there is mounting evidence that the complex mechanisms of RNAs are better understood when structural information on various alternative conformers or states as well as on dynamical transitions among them are considered [9,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Exploring the RNA folding energy landscape using scalable distributed cyberinfrastructure

Kim

Huang

Maddineni

et al. 2010

Proceedings of the 19th ACM International Symposium on High Performance Distributed Computing

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The increasing significance of RNAs in transcriptional or post-transcriptional gene regulation processes has generated considerable interest towards the prediction of RNA folding and its sensitivity to environmental factors. We use Boltzmann-weighted sampling to generate RNA secondary structures, which are used to characterize the energy landscape, via the distributions of energies and base-pair distances. Depending upon the length of an RNA, the number of sequences investigated, and the sample size of generated structures -generating and analyzing sufficient samples can be computationally challenging. We introduce and develop a lightweight and extensible runtime environment that is effective across a range of RNA sizes and other parameters, as well as over a range of infrastructure -from traditional HPC grids to clouds, without requiring any changes at the application or user level. The Adaptive Distributed Application Management System (ADAMS) is built upon an extensbile and interoperable pilot-job and supports the concurrent execution of a broad range of task sizes across a range of infrastructure. We use ADAMS to investigate the folding energy landscape for two RNA systems of different sizes: a set of S-adenosyl methionine (SAM) binding RNA sequences known as SAM-I riboswitches and the S gene of the Bovine Corona Virus (BCoV) RNA genome that comprises 4092 nucleotides. Results of the energy and base-pair distance distributions suggest different energy landscapes, implying different folding dynamics. With obtained results, we demonstrated the possibility of utilizing this protocol to explore microscopic origins for reported sequence-dependent variation of binding affinity and gene expression in the two RNA systems.

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Correlation between three-dimensional structure and chemical reactivity of transfer RNA

Cited by 62 publications

References 12 publications

Conversation of the Molecular Structure of Yeast Phenylalanine Transfer RNA in Two Crystal Forms

Conversation of the Molecular Structure of Yeast Phenylalanine Transfer RNA in Two Crystal Forms

A Study of the Thermal Unfolding of Escherichia coli Phenylalanine Transfer RNA by Chemical Modification at Elevated Temperatures

Exploring the RNA folding energy landscape using scalable distributed cyberinfrastructure

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