Mass spectrometry and ion mobility spectrometry of G-quadruplexes. A study of solvent effects on dimer formation and structural transitions in the telomeric DNA sequence d(TAGGGTTAGGGT)

Ferreira, Rubén; Marchand, Adrien; Gabelica, Valérie

doi:10.1016/j.ymeth.2012.03.021

Cited by 50 publications

(71 citation statements)

References 50 publications

(63 reference statements)

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“…In the M 3À monomeric forms of TBA and TBA2G, we found 0, 1 or 2 ammonium ions bound to TBAs, in agreement with previous results [42]. For the charge state 3À, the collision cross-section (CCS) did not change with the ammonium ion count [43].…”

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confidence: 91%

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Specific loop modifications of the thrombin‐binding aptamer trigger the formation of parallel structures

et al. 2014

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Guanine-rich sequences show large structural variability, with folds ranging from duplex to triplex and quadruplex helices. Quadruplexes are polymorphic, and can show multiple stoichiometries, parallel and antiparallel strand alignments, and different topological arrangements. We analyze here the equilibrium between intramolecular antiparallel and intermolecular parallel G-quadruplexes in the thrombin-binding aptamer (TBA) sequence. Our theoretical and experimental studies demonstrate that an apparently simple modification at the loops of TBA induces a large change in the monomeric antiparallel structure of TBA to yield a parallel G-quadruplex showing a novel T-tetrad. The present results illustrate the extreme polymorphism of G-quadruplexes and the ease with which their conformation in solution can be manipulated by nucleotide modification.Abbreviations

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Section: àsupporting

confidence: 91%

“…TBA and TBA2G [4,13] were also examined with thermal denaturation and CD in the presence of a dehydrating agent (MeOH), which is known to favor compact structures (such as the parallel quadruplex) [41,42]. The thermal stability of TBA2G [4,13] was higher than that of TBA, and increased with the percentage of MeOH in both compounds (Table S6).…”

Section: Resultsmentioning

confidence: 99%

Specific loop modifications of the thrombin‐binding aptamer trigger the formation of parallel structures

et al. 2014

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“…We chose the parallel-stranded [dTGGGGT] 4 G-quadruplex DNA structure ( Fig. 1) because (1) starting atomic coordinates of [dTGGGGT] 4 are available from X-ray crystallography, [11][12][13][14] (2) the same molecular assembly was studied by nuclear magnetic resonance (NMR) as well and presents the same G-quadruplex core arrangement, although the thymine placement differs, with evidence for T-T interactions, [15][16][17] and (3) the central guanine-rich core remains very rigid in the gas phase, [18][19][20][21] thanks to the preservation of the G-quartet hydrogen bonds and to the coordination of three 711 ammonium cations in-between the four guanine G-quartets. Only the position of thymines in the gas phase is less certain.…”

Section: Introductionmentioning

confidence: 99%

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

D’Atri¹,

Porrini²,

Rosu³

et al. 2015

J. Mass Spectrom.

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Ion mobility spectrometry experiments allow the mass spectrometrist to determine an ion's rotationally averaged collision cross section Ω EXP . Molecular modelling is used to visualize what ion three-dimensional structure(s) is(are) compatible with the experiment. The collision cross sections of candidate molecular models have to be calculated, and the resulting Ω CALC are compared with the experimental data. Researchers who want to apply this strategy to a new type of molecule face many questions: (1) What experimental error is associated with Ω EXP determination, and how to estimate it (in particular when using a calibration for traveling wave ion guides)? (2) How to generate plausible 3D models in the gas phase? (3) Different collision cross section calculation models exist, which have been developed for other analytes than mine. Which one(s) can I apply to my systems? To apply ion mobility spectrometry to nucleic acid structural characterization, we explored each of these questions using a rigid structure which we know is preserved in the gas phase: the tetramolecular G-quadruplex [dTGGGGT] 4 , and we will present these detailed investigation in this tutorial. Additional supporting information may be found in the online version of this article at the publisher's web site.Keywords: ion mobility spectrometry; collision cross section; structure; nucleic acids; simulations; molecular modeling; gas-phase ion structure IntroductionElectrospray mass spectrometry (ESI-MS) in native conditions can preserve the structures of biomolecules and separate them according to their mass-to-charge ratios. [1,2] Ion mobility spectrometry (IMS) separates ions according to their size-to-charge ratios in the gas-phase. [3][4][5][6] Size is related to the mass (or number of atoms) and to the three-dimensional shape of a molecule. Therefore, by hyphenating IMS to mass spectrometry (IM-MS), one can sort ions according to both mass and shape. The challenge is to decipher structural information from ion mobility experiments. [7][8][9] The physical quantity characterizing the shape is the collision cross section (CCS), [10] which will be introduced in more detail in the Section on Ion mobility and collision cross sections. The present tutorial clarifies how to interpret CCS measurements in terms of three-dimensional structure for ions larger than 100 atoms extracted from the solution by electrospray ionization (ESI). The gold standard is to match CCSs experimentally obtained from IMS with CCSs calculated for modelling three-dimensional structures of the ion of interest. We will discuss the factors that can affect the precision (reproducibility) and accuracy in both the measurements and the calculations. Understanding each of these factors is crucial to interpret quantitative matches confidently and assess the meaningfulness of structural assignments.On the experimental side, we will describe the determination of CCS from traveling wave ion mobility spectrometers and from drift tube ion mobility spectrometers, with example data recorde...

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“…For analysis, 10 mM of RNA was measured in 100 mM TMAA/20% methanol (v/v) 32,59 and potassium concentrations were adjusted using 2 mM or 20 mM potassium acetate (KOAc) stock solution. Native MS was carried out on an LCT (Waters, UK and MS Vision, The Netherlands) modified for high mass experiments 60 with a nano-ESI (electrospray ionization) source in negative ion mode.…”

Section: Native Mass Spectrometrymentioning

confidence: 99%

Structure and target interaction of a G-quadruplex RNA-aptamer

et al. 2016

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G-quadruplexes have recently moved into focus of research in nucleic acids, thereby evolving in scientific significance from exceptional secondary structure motifs to complex modulators of gene regulation. Aptamers (nucleic acid based ligands with recognition properties for a specific target) that form Gquadruplexes may have particular potential for therapeutic applications as they combine the characteristics of specific targeting and Gquadruplex mediated stability and regulation. We have investigated the structure and target interaction properties of one such aptamer: AIR-3 and its truncated form AIR-3A. These RNA aptamers are specific for human interleukin-6 receptor (hIL-6R), a key player in inflammatory diseases and cancer, and have recently been exploited for in vitro drug delivery studies. With the aim to resolve the RNA structure, global shape, RNA: protein interaction site and binding stoichiometry, we now investigated AIR-3 and AIR-3A by different methods including RNA structure probing, Small Angle X-ray scattering and microscale thermophoresis. Our findings suggest a broader spectrum of folding species than assumed so far and remarkable tolerance toward different modifications. Mass spectrometry based binding site analysis, supported by molecular modeling and docking studies propose a general Gquadruplex affinity for the target molecule hIL-6R.

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Mass spectrometry and ion mobility spectrometry of G-quadruplexes. A study of solvent effects on dimer formation and structural transitions in the telomeric DNA sequence d(TAGGGTTAGGGT)

Cited by 50 publications

References 50 publications

Specific loop modifications of the thrombin‐binding aptamer trigger the formation of parallel structures

Specific loop modifications of the thrombin‐binding aptamer trigger the formation of parallel structures

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

Structure and target interaction of a G-quadruplex RNA-aptamer

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