Folding of Protein Ions in the Gas Phase after Cation-to-Anion Proton-Transfer Reactions

Laszlo, Kenneth J.; Munger, Eleanor B.; Bush, Matthew F.

doi:10.1021/jacs.6b04282

Cited by 82 publications

(183 citation statements)

References 75 publications

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“…Charge states +6, +7, and +8 measured on the UCSB drift tube and the soft-tuned trapped IMS system at FSU are consistent with the solution structure of ubiquitin while solution structures are not retained when the trapped IMS system is not carefully “soft”-tuned. (Note that cross sections of “inside-out” structures for charge states +4 or +5 are similar to the solution structure; see reference (55) for details.) Ubiquitin cross sections were taken from references (53), (50), and (54).…”

Section: Figurementioning

confidence: 93%

“…The cross sections of charge states 6,7, and 8 are significantly larger—indicative of substantial collision-induced unfolding of ubiquitin ions during the measurement—when high DC and RF fields are used and the ESI desolvation gas is heated in excess of 370K in a trapped IMS device (54). Charge states 4 and 5, which are not generally observed under native conditions (50,53), should not be considered indicative of the ubiquitin solution structure as cross sections of their “inside-out” gas-phase structures are not distinguishable from that of the ubiquitin solution structure (55). …”

Section: Softness Of Ims-ms Measurements: the Ability To Study Biologmentioning

confidence: 99%

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The Solution Assembly of Biological Molecules Using Ion Mobility Methods: From Amino Acids to Amyloid β-Protein

Bleiholder

Bowers

2017

Annual Rev. Anal. Chem.

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Ion mobility spectrometry-mass spectrometry (IMS-MS) methods are increasingly used to study noncovalent assemblies of peptides and proteins. This review focuses on the noncovalent self-assembly of amino acids and peptides, systems at the heart of the amyloid process that play a central role in a number of devastating diseases. Three different systems are discussed in detail: the 42-residue peptide amyloid-β42 implicated in the etiology of Alzheimer's disease, several amyloid-forming peptides with 6–11 residues, and the assembly of individual amino acids. We also discuss from a more fundamental perspective the processes that determine how quickly proteins and their assemblies denature when the analyte ion has been stripped of its solvent in an IMS-MS measurement and how to soften the measurement so that biologically meaningful data can be recorded.

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Section: Figurementioning

confidence: 93%

Section: Softness Of Ims-ms Measurements: the Ability To Study Biologmentioning

confidence: 99%

The Solution Assembly of Biological Molecules Using Ion Mobility Methods: From Amino Acids to Amyloid β-Protein

Bleiholder

Bowers

2017

Annual Rev. Anal. Chem.

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“…40 Selected CAPTR products were activated by increasing the dc bias between trap and mobility cells. 29 …”

Section: Methodsmentioning

confidence: 99%

“…36 Differences between CAPTR and other methods for reducing the charge states of protein ions have been discussed previously. 29,36 …”

Section: Introductionmentioning

confidence: 99%

Effects of Solution Structure on the Folding of Lysozyme Ions in the Gas Phase

2017

Self Cite

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The fidelity between the structures of proteins in solution and protein ions in the gas phase is critical to experiments that use gas-phase measurements to infer structures in solution. Here we generate ions of lysozyme, a 129-residue protein whose native tertiary structure contains four internal disulfide bonds, from three solutions that preserve varying extents of the original native structure. We then use cation-to-anion proton-transfer reactions (CAPTR) to reduce the charge states of those ions in the gas phase and ion mobility to probe their structures. The collision cross section (Ω) distributions of each CAPTR product depends to varying extents on the original solution, the charge state of the product, and the charge state of the precursor. For example, the Ω distributions of the 6+ ions depend strongly on the original solutions conditions and to a lesser extent on the charge state of the precursor. Energy-dependent experiments suggest that very different structures are accessible to disulfide-reduced and disulfide-intact ions, but similar Ω distributions are formed at high energy for disulfide-intact ions from denaturing and from aqueous conditions. The Ω distributions of the 3+ ions are all similar but exhibit subtle differences that depend more strongly on the original solutions conditions than other factors. More generally, these results suggest that specific CAPTR products may be especially sensitive to specific elements of structure in solution.

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“…2 Both IM-MS techniques have been applied to a broad scope of species to elucidate structural information, including small drug-like molecules, 3,4 carbohydrates, 5,6 DNA and RNA, 7 proteins 8,9 and protein complexes. 9 It has also used to study protein unfolding, 8 refolding, 9,10 proton and electron transfer mechanisms 11,12 and solvent adduct effects on the protein structure. 13 A great advantage of IM-MS is the ability to elucidate detailed structural information about the studied system by separation of isomers, 3 protomers 14 and conformers.…”

Section: Mason-schamp Equation Whereas Travelling Wave Im-ms (Twims-mentioning

confidence: 99%

A Careful Consideration of the Influence of Structure, Partial charges and Basis Sets on Collision Cross Sections of Monosaccharides when Comparing Values from DFT Calculated Conformers to those Obtained Experimentally

Migas

Gray

Flitsch

et al. 2017

Preprint

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Molecular modelling is routinely employed to assign 3D structures to collision cross sections (CCSs) derived from ion mobility mass spectrometry experiments (IM-MS). The assignment of model structures to the experimental CCSs remains an ambiguous task, where one of several methods may be used to obtain a CCS from a given set of coordinates. The most reliable of the commonly used techniques, the Trajectory Method, starts with atomic coordinates which can be accompanied by partial atomic charges, obtained using ab initio methods. Here, we use lithiated α-and β-glucose ions as exemplar molecules to detect the effect conformational modification and changes to the partial charge distribution have on computed collision cross sections. Six popular charge schemes (Mulliken, APT, CHelpG, MK, HLY and NPA) were examined in combination with three functionals (Hartree-Fock, B3LYP and M05) and five basis sets (STO-3G, 3-21G, 6-31G, 6-31+G and 6-31G*) on twenty unique structures.Our findings indicate that molecular conformation makes a significant contribution to fluctuations of partial charges in Electrostatic Potential (ESP) and Mulliken charge scheme; Partial charges derived using Natural Population Analysis (NPA) and ESP methods are largely independent of functional and basis set selection; and both selection of the charge scheme and functional/basis set combination play a large role in the resultant CCS, often causing few percent fluctuations in the computed values.

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Folding of Protein Ions in the Gas Phase after Cation-to-Anion Proton-Transfer Reactions

Cited by 82 publications

References 75 publications

The Solution Assembly of Biological Molecules Using Ion Mobility Methods: From Amino Acids to Amyloid β-Protein

The Solution Assembly of Biological Molecules Using Ion Mobility Methods: From Amino Acids to Amyloid β-Protein

Effects of Solution Structure on the Folding of Lysozyme Ions in the Gas Phase

A Careful Consideration of the Influence of Structure, Partial charges and Basis Sets on Collision Cross Sections of Monosaccharides when Comparing Values from DFT Calculated Conformers to those Obtained Experimentally

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