Stability of secondary structural elements in a solvent-free environment: the α helix

Kaltashov, Igor A.; Fenselau, Catherine

doi:10.1002/(sici)1097-0134(199702)27:2<165::aid-prot2>3.0.co;2-f

Cited by 64 publications

(64 citation statements)

References 36 publications

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“…Other than the "end effects", the correlations between the stability maps in the condensed phases and gas phase for 3ϩ and 4ϩ melittin ions indicate that gaseous melittin ions up to four charges have a similar secondary structure as melittin in the condensed phases. This conclusion is consistent with the previous result that triply charged melittin retains its condensed phase secondary structure in the gas phase, as studied by intercharge repulsion measurement and molecular mechanics calculation [51]. For the 5ϩ melittin ion, as seen in Figure 3, a major conformational change occurs as indicated by the flexible Nterminal and C-terminal regions.…”

Section: Gas-phase Conformation Of Melittinsupporting

confidence: 92%

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Peptide conformation in gas phase probed by collision-induced dissociation and its correlation to conformation in condensed phases

Zhang

Bordas-Nagy

2006

J. Am. Soc. Mass Spectrom.

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A kinetic peptide fragmentation model for quantitative prediction of peptide CID spectra in an ion trap mass spectrometer has been reported recently. When applying the model to predict the CID spectra of large peptides, it was often found that the predicted spectra differed significantly from their experimental spectra, presumably due to noncovalent interactions in these large polypeptides, which are not considered in the fragmentation model. As a result, site-specific quantitative information correlated to the secondary/tertiary structure of an ionized peptide may be extracted from its CID spectrum. To extract this information, the kinetic peptide fragmentation model was modified by incorporating conformation-related parameters. These parameters are optimized for best fit between the predicted and the experimental spectrum. A conformational stability map is then generated from these conformation-related parameters. Analysis of a few bioactive ␣-helical peptides including melittin, glucagon and neuropeptide Y by this technique demonstrated that their stability maps in the gas phase correlate strongly to their secondary structures in the condensed phases. H ow a one-dimensional polypeptide chain folds into a three-dimensional biologically active form is one of the greatest challenges in life science. One approach to understand the role of solvent in this folding process is to study protein conformation in the gas phase, in the absence of solvent. Understanding the relationship between the gas-phase and condensed-phase protein conformations will also help us evaluate mass spectrometry as a tool for studying protein noncovalent interactions.Protein conformation and dynamics in the condensed phases has traditionally been studied by X-ray crystallography [1], nuclear magnetic resonance spectroscopy [2-4], circular dichroism [5], etc., as well as hydrogen exchange [6,7] and its recent combination with mass spectrometry [8 -11]. Compared to the large amount of knowledge about protein conformation in the condensed phases, little is known about the conformation of proteins in gas phase, largely due to the lack of structurally informative techniques to study gasphase proteins [12,13]. Techniques including collision cross-section measurement [14 -21] and hydrogen/deuterium exchange [22][23][24][25][26][27] have been used to study protein gas-phase conformation, but they provide limited structural details. Recently, electron-capture dissociation (ECD) combined with Fourier-transform ion cyclotron resonance mass spectrometry shed some light on the structural details of gaseous proteins [28 -30]. This paper reports a new methodology, based on collisioninduced dissociation (CID) spectra of peptides or proteins, for structural details of gaseous peptides or proteins that compliments the information obtained from ECD and other conventional techniques. Smith and coworkers first demonstrated that CID spectra could be used as a probe for protein conformation [31]. Cassady and Carr also used CID to probe conformation of ubiquitin i...

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Section: Gas-phase Conformation Of Melittinsupporting

confidence: 92%

“…In the absence of solvent, intramolecular hydrogen bonds are much stronger because of the lack of competition from polar solvent molecules. In that respect, vacuum can be viewed as an ultimate nonpolar environment [51].…”

Section: Vacuum As a Nonpolar Environmentmentioning

confidence: 99%

Peptide conformation in gas phase probed by collision-induced dissociation and its correlation to conformation in condensed phases

Zhang

Bordas-Nagy

2006

J. Am. Soc. Mass Spectrom.

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“…In organic solvents, melittin exists in an ␣-helical form with two ␣-helices, one at each end, connected by a nonhelical hinge around Pro14 [40]. In their mass-analyzed ion kinetic energy (MIKE) spectrometry studies, Kaltashov and Fenselau have shown that triply charged melittin ion probably retains this helical structure in the gas-phase [41]. The conclusion was drawn based on a single parameter of intercharge distance between Lys7 and Arg22/24, the proposed charged sites, as determined by kinetic energy release accompanying fragmentation.…”

Section: Correlation Of Fragment Ion Survival Ratios With Gas Phase Cmentioning

confidence: 99%

Use of a double resonance electron capture dissociation experiment to probe fragment intermediate lifetimes

Lin

Cournoyer

O’Connor

2006

J. Am. Soc. Mass Spectrom.

102

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The relative abundances of fragment ions in electron capture dissociation (ECD) are often greatly affected by the secondary and tertiary structures of the precursor ion, and have been used to derive the gas-phase conformations of the protein ions. In this study, it is found that resonance ejection of the charge reduced molecular ion during ECD resulted in significant changes in many fragment ion populations. The ratio of the ion peak intensities in the double resonance (DR)-ECD to that in the normal ECD experiment can be used to calculate the lifetime of the radical intermediates from which these fragments are derived. These lifetimes are often in the ms range, a time sufficiently long to facilitate multiple free radical rearrangements. These ratios correlate with the intramolecular noncovalent interactions in the precursor ion, and can be used to deduce information about the gas-phase conformation of peptide ions. DR-ECD experiments can also provide valuable information on ECD mechanisms, such as the importance of secondary electron capture and the origin of c·/z ions. (J Am Soc Mass

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“…In order for the internal exchange to occur, the two exchanging sites must come into direct contact with one another (akin to a bimolecular H/D exchange reaction in the gas phase). Lack of such flexibility due to either (partial) retention of the solution structure in the gas phase (121) or the "cementing" role of metal cations (122) would limit the extent of scrambling. These simple considerations suggest that the best chance of avoiding hydrogen scrambling in the gas phase would result from employing fast (high-energy) ion fragmentation methods and using solution conditions that allow proteins to remain (partially) structured.…”

Section: "Top-down" Approaches To Probing the Local Structure Of Intementioning

confidence: 99%

Mass Spectrometry‐Based Approaches to Study Biomolecular Dynamics: Equilibrium Intermediates

2005

Mass Spectrometry in Biophysics

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In the preceding chapter, we surveyed various MS-based approaches to study higher-order structure of proteins under native conditions. For many decades, such well-defined and highly organized structures were thought of as the most important (if not the only) determinants of protein function. Protein folding was often considered a linear process leading from fully unstructured (and, therefore, dysfunctional) states to the highly organized native (function-competent) state. The advent of NMR has changed our perception of what "functional" protein states are, with the realization that native proteins are very dynamic species. Perhaps the most illustrious examples of the intimate link between protein dynamics and function were found in enzyme catalysis, where the chemical conversion of substrate to product is often driven by relatively small-scale dynamic events within (and often beyond) the active site. It became clear in recent years that large-scale macromolecular dynamics may also be an important determinant of protein function. A growing number of proteins are found to be either partially or fully unstructured under native conditions, and such flexibility (intrinsic disorder) appears to be vital for their function. Proteins that do have native folds under physiological conditions can also exhibit dynamic behavior via local structural fluctuations or by sampling alternative (higher-energy or "activated") conformations transiently. In many cases, such activated (non-native) states are functionally important despite their low Boltzmann weight. Realization of the importance of transient non-native protein structures for their function not only greatly advanced our understanding of processes as diverse as recognition, signaling, and transport Mass

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Stability of secondary structural elements in a solvent-free environment: the α helix

Cited by 64 publications

References 36 publications

Peptide conformation in gas phase probed by collision-induced dissociation and its correlation to conformation in condensed phases

Peptide conformation in gas phase probed by collision-induced dissociation and its correlation to conformation in condensed phases

Use of a double resonance electron capture dissociation experiment to probe fragment intermediate lifetimes

Mass Spectrometry‐Based Approaches to Study Biomolecular Dynamics: Equilibrium Intermediates

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