Folding and unfolding of helix-turn-helix motifs in the gas phase

Zilch, Lloyd W.; Kaleta, David T.; Kohtani, Motoya; Krishnan, Ranjani; Jarrold, Martin F.

doi:10.1016/j.jasms.2007.03.027

Cited by 32 publications

(38 citation statements)

References 21 publications

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“…ECD FT-ICR MS of six doubly protonated horse myoglobin tryptic fragments ( [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], [32][33][34][35][36][37][38][39][40][41][42] Figure S2) and with vibrational activation ( Figure 5) confirm preferential and sometimes periodic product ion formation from peptides with mainly ␣-helical or ␤-turn secondary structure in solution (before protein digestion). Predominantly z-ions are observed because of preferential charge retention at the C-terminal Lys or Arg basic residue upon electron capture, as expected for doubly charged tryptic peptides.…”

Section: Ecd Of Doubly Charged Amphipathic Peptidesmentioning

confidence: 99%

“…Supplementary Figure S2 demonstrates preferential cleavage at the NOC ␣ bond number 4 (z nϪ3 ) for fragments with a distinct ␣-helical or turn structure at the N-terminus (fragments [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] -118]). The periodicity is more pronounced in AI-ECD data ( Figure 5), demonstrating a period of 3 amino acids for the specified myoglobin fragments.…”

Section: Ecd Of Doubly Charged Amphipathic Peptidesmentioning

confidence: 99%

“…Advances in ECD/ETD applications have been accompanied by development of an array of other MS-based techniques and methods to address specific peptide and protein conformation-induced effects. In particular, ion mobility mass spectrometry (IM MS) has been used for targeted and high-throughput characterization of ␣-helical peptide properties in the gas phase [27][28][29]. The combination of mass spectrometry with gas-phase ultraviolet/infrared (UV/IR) spectroscopy has provided evidence for helical structure in gaseous protein ions [30] and poly-Ala peptides [31].…”

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confidence: 99%

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Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Hamidane

Tsybin

et al. 2009

J. Am. Soc. Mass Spectrom.

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The rules for product ion formation in electron capture dissociation (ECD) mass spectrometry of peptides and proteins remain unclear. Random backbone cleavage probability and the nonspecific nature of ECD toward amino acid sequence have been reported, contrary to preferential channels of fragmentation in slow heating-based tandem mass spectrometry. Here we demonstrate that for amphipathic peptides and proteins, modulation of ECD product ion abundance (PIA) along the sequence is pronounced. Moreover, because of the specific primary (and presumably secondary) structure of amphipathic peptides, PIA in ECD demonstrates a clear and reproducible periodic sequence distribution. On the one hand, the period of ECD PIA corresponds to periodic distribution of spatially separated hydrophobic and hydrophilic domains within the peptide primary sequence. On the other hand, the same period correlates with secondary structure units, such as ␣-helical turns, known for solution-phase structure. Based on a number of examples, we formulate a set of characteristic features for ECD of amphipathic peptides and proteins: (1) periodic distribution of PIA is observed and is reproducible in a wide range of ECD parameters and on different experimental platforms; (2) local maxima of PIA are not necessarily located near the charged site; (3) ion activation before ECD not only extends product ion sequence coverage but also preserves ion yield modulation; (4) the most efficient cleavage (e.g. global maximum of ECD PIA distribution) can be remote from the charged site; (5) the number and location of PIA maxima correlate with amino acid hydrophobicity maxima generally to within a single amino acid displacement; and (6) preferential cleavage sites follow a selected hydrogen spine in an ␣-helical peptide segment. Presently proposed novel insights into ECD behavior are important for advancing understanding of the ECD mechanism, particularly the role of peptide sequence on PIA. An improved ECD model could facilitate protein sequencing and improve identification of unknown proteins in proteomics technologies. In structural biology, the periodic/preferential product ion yield in ECD of ␣-helical structures potentially opens the way toward de novo site-specific secondary structure determination of peptides and proteins in the gas phase and its correlation with solution-phase structure. (J Am Soc Mass Spectrom 2009, 20, 1182-1192) © 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry B iomolecular fragmentation in the gas phase by electron capture dissociation (ECD) [1-3] and electron-transfer dissociation (ETD) [4,5] is particularly attractive for mass spectrometry (MS)-based peptide and protein structural analysis. In ECD/ETD, interaction of a multiply charged peptide or protein ion with an electron/anion results in cleavage of NOC ␣ bonds along the peptide backbone, including chargesite-remote backbone cleavages [2]. ECD is useful for peptide sequence tag generation on a chromatographic timescale for protein identificat...

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Section: Ecd Of Doubly Charged Amphipathic Peptidesmentioning

confidence: 99%

Section: Ecd Of Doubly Charged Amphipathic Peptidesmentioning

confidence: 99%

mentioning

confidence: 99%

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Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Hamidane

Tsybin

et al. 2009

J. Am. Soc. Mass Spectrom.

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“…[4] From fundamental studies of peptides and proteins it is clear that folded structure, present in bulk solution, upon transfer into the gas phase, can retain native-like compact states but may unfold when activated or stored. [1,5] Similarly assemblies of globular proteins studied by IM-MS have been found to retain defined topological arrangements, [6] with unfolding of subunits being linked to activation in the gas phase. High charge states of proteins and their complexes in the gas phase are associated with extended unfolded structures, analogous to unfolding processes induced by protonation in solution.…”

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confidence: 99%

Intrinsically Disordered p53 and Its Complexes Populate Compact Conformations in the Gas Phase

et al. 2012

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Spontaneous shrinking: the intrinsically disordered tumor suppressor protein p53 was analyzed by using a combination of ion mobility mass spectrometry and molecular dynamics simulations. Structured p53 subdomains retain their overall topology upon transfer into the gas phase. When intrinsically disordered segments are introduced into the protein sequence, however, the complex spontaneously collapses in the gas phase to a compact conformation.

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“…Ion mobility measurements have been used to explore molecular dynamics and follow structural changes occurring on the millisecond time scale by comparison to CCS of candidate structures under controlled conditions (e.g., reactive/inert, polar/nonpolar bath gas at different temperatures). [10, 19, 20] A variety of theoretical models have been developed to calculate CCS in monoatomic and polyatomic bath gases (e.g., the rigid sphere model and the polarization limit, 12-6-4 and 12-4 potential models and forms thereof, [21–23] non specular scattering models [24] and collision integral based models as the projection approximation,[2, 25] the exact hard sphere scattering [26] and the trajectory methods [27–29]). However, a major difficulty in simulating processes occurring in IMS experiments is the long time scale over which structural rearrangements may occur (approximately a few milliseconds) whereas molecular dynamics simulations are typically limited to nanoseconds.…”

Section: Introductionmentioning

confidence: 99%

Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space

Schenk

Nau

Fernandez-Lima

2015

Int. J. Ion Mobil. Spec.

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The ability to correlate experimental ion mobility data with candidate structures from theoretical modeling provides a powerful analytical and structural tool for the characterization of biomolecules. In the present paper, a theoretical workflow is described to generate and assign candidate structures for experimental trapped ion mobility and H/D exchange (HDX-TIMS-MS) data following molecular dynamics simulations and statistical filtering. The applicability of the theoretical predictor is illustrated for a peptide and protein example with multiple conformations and kinetic intermediates. The described methodology yields a low computational cost and a simple workflow by incorporating statistical filtering and molecular dynamics simulations. The workflow can be adapted to different IMS scenarios and CCS calculators for a more accurate description of the IMS experimental conditions. For the case of the HDX-TIMS-MS experiments, molecular dynamics in the “TIMS box” accounts for a better sampling of the molecular intermediates and local energy minima.

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Folding and unfolding of helix-turn-helix motifs in the gas phase

Cited by 32 publications

References 21 publications

Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins

Intrinsically Disordered p53 and Its Complexes Populate Compact Conformations in the Gas Phase

Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space

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