Retention of Native Protein Structures in the Absence of Solvent: A Coupled Ion Mobility and Spectroscopic Study

Seo, Jongcheol; Hoffmann, Waldemar; Warnke, Stephan; Bowers, Michael T.; Pagel, Kevin; Helden, Gert von

doi:10.1002/anie.201606029

Cited by 117 publications

(120 citation statements)

References 36 publications

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“…These results indicate the IMS-MS/FEL technique developed in the FHI in Berlin has a bright future in the analysis of the secondary structure of peptides and proteins and their assemblies adding a very powerful compliment to the ability of IMS-MS methods to directly measure tertiary structure of monomers and the quaternary structure of assemblies (36,83). …”

Section: Case 2: Peptide Assembly and The Amyloid Paradigmmentioning

confidence: 94%

“…In a collaborative effort with the Eisenberg group we chose to apply the IMS-MS technique to a series of eleven residue fragments of the Aβ42 peptide: Aβ(24–34), Aβ(25–35) and Aβ(26–36). The Aβ(25–35) peptide fragment is known to exist in the brain and to be cytotoxic (79) and has been studied by our group previously for different purposes (80).…”

Section: Case 2: Peptide Assembly and The Amyloid Paradigmmentioning

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: Case 2: Peptide Assembly and The Amyloid Paradigmmentioning

confidence: 94%

Section: Case 2: Peptide Assembly and The Amyloid Paradigmmentioning

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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“…13–15 For example, recent ion mobility spectrometry and infrared action spectroscopy experiments indicate that helical and β -sheet secondary structures of small proteins can be retained in the gas phase for low-charge ions. 16 Re-collected ions of tobacco mosaic virus were able to infect tobacco plants 17 and ions of endospores of Bacillus subtilis were able to be cultured even after high-velocity impacts with surfaces, 18 establishing that ESI can even preserve biological function. Progress in native mass spectrometry 19,20 and how the structures of protein ions can evolve in the gas phase 21,22 have been reviewed elsewhere.…”

Section: Introductionmentioning

confidence: 99%

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

2017

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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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“…This agrees well with the predominantly helical structure of the A state (A) but does not support the β-sheet containing native solution structure (N), which is similar in size to the most compact ions found for ions with charges below 7+ [7,24]. A recent study suggests that it is possible to transfer native structural elements into the gas phase under native, buffered solution conditions [25]. The hereinvestigated compact structures of ubiquitin, however, were generated from denaturing solvents containing methanol, which favors the partially unfolded A state in solution [26,27].…”

Section: Ubiquitin -From Compact To Stringmentioning

confidence: 52%

From Compact to String—The Role of Secondary and Tertiary Structure in Charge-Induced Unzipping of Gas-Phase Proteins

Warnke

Hoffmann

Seo

et al. 2016

J. Am. Soc. Mass Spectrom.

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In the gas phase, protein ions can adopt a broad range of structures, which have been investigated extensively in the past using ion mobility-mass spectrometry (IM-MS) based methods. Compact ions with low number of charges undergo a Coulomb-driven transition to partially folded species when the charge increases and finally form extended structures with presumably little or no defined structure when the charge state is high. However, with respect to the secondary structure, IM-MS methods are essentially blind. Infrared (IR) spectroscopy, on the other hand, is sensitive to such structural details and there is increasing evidence that helices as well as β-sheet-like structures can exist in the gas phase, especially for ions in low charge states. Very recently, we showed that also the fully extended form of highly charged protein ions can adopt a distinct type of secondary structure that features a characteristic C5-type hydrogen bond pattern. Here we use a combination of IM-MS and IR spectroscopy to further investigate the influence of the initial, native conformation on the formation of these structures. Our results indicate that when intramolecular Coulomb-repulsion is large enough to overcome the stabilization energies of the genuine secondary structure, all proteins, regardless of their sequence or native conformation, form C5-type hydrogen bond structures. Furthermore, our results suggest that in highly charged proteins the positioning of charges along the sequence is only marginally influenced by the basicity of individual residues.In the gas-phase environment of a mass spectrometer, proteins can adopt a broad range of distinct structures. When electrosprayed from native, buffered solutions especially large proteins and protein complexes are known to retain features of their condensed-phase conformation -a fact that found broad application in the field of native mass spec-

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Retention of Native Protein Structures in the Absence of Solvent: A Coupled Ion Mobility and Spectroscopic Study

Cited by 117 publications

References 36 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

From Compact to String—The Role of Secondary and Tertiary Structure in Charge-Induced Unzipping of Gas-Phase Proteins

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