Stability of secondary structural elements in a solvent-free environment. II: The β-pleated sheets

Abstract

The stability of single ␤-strands and multistrand ␤-pleated sheets as elements of secondary structure is examined in the absence of intermolecular interactions. Such experimental conditions (e.g., complete removal of solvent molecules and counterions) are achieved by placing the peptide ions in the gas phase. The metastable multiply-charged peptide ions produced by electrospray ionization undergo unimolecular dissociation. Intercharge repulsion within the precursor ions gives rise to the elevated kinetic energy of fragment ions, which is measured using Massanalyzed Ion Kinetic Energy (MIKE) spectrometry. Intercharge distances calculated based on these measurements are compared to the numbers derived from molecular mechanics calculations with charge site assignments based on relative proton affinities. Evidence is presented suggesting that single ␤-strands form collapsed structures in the absence of solvents, while multistrand ␤-pleated sheets are likely to retain ''native-like'' secondary structures under the same conditions. These results indicate that intramolecular hydrogen bonds are the major factor determining the three-dimensional arrangements of polypeptides in the gas phase, compensating both long-and short-range electrostatic repulsions. This is in good agreement with our earlier findings (Proteins 27:165-170, 1997) concerning stability of helical conformation of melittin in the absence of solvent. Proteins Suppl. 2:22-27, 1998.

Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulations

“…However, those results do not provide information on the relative free energy contribution of van der Waals and electrostatic terms to the stability of a bhairpin. It is of interest that mass spectrometric studies (Li et al, 1998) have shown recently that the hydrogen-bonding interactions are important for stabilizing b-sheets in a solvent-free environment, where there is no competition with hydrogen bonds to the solvent.…”

Ion mobility-mass spectrometry applied to cyclic peptide analysis: Conformational preferences of gramicidin S and linear analogs in the gas phase

“…This investigation is one of the few to report evidence of stable sheet (hairpin) structures in the gas-phase [37,38], and our future work will focus on the gas-phase structure and dynamics of GS and related systems. Cyclic peptides in particular, as molecular systems having a somewhat forced geometry, are particularly interesting as gas-phase standards for peptide structure, as the companion MD simulations that are necessary for the determination of structural detail from collision cross-section measurements are simplified by the restricted degrees of freedom for the peptide system.…”

Contact Regions in the Dimer of Alzheimer β-Amyloid Domain [1–28] Studied by Mass Spectrometry

“…Previously, measurements of the kinetic energy released in the decomposition of electrosprayed multiply-charged polypeptides have been correlated with transition state geometries 57,58 to support the idea that melittin can retain its a-helical conformation when it is transferred from solution into the gas phase, 46 and that multistrand b-sheets can also maintain their extended conformations throughout the electrospray process. 47 Stability of the a-helix conformation of melittin in the gas phase has been further confirmed by ion mobility measurements of its cross-section. 59 This work reports the first time that kinetic energy release measurements have been made on a biologically relevant polypeptide complex, and the first time that kinetic energy release measurements have been used to define the interface of a polypeptide dimer.…”