“Wet” Versus “Dry” Folding of Polyproline

• Published in: Journal of the American Society for Mass Spectrometry 2016-06, Vol.27 (6), p.1037-1047
• Main Authors: Shi, Liuqing, Holliday, Alison E., Bohrer, Brian C., Kim, Doyong, Servage, Kelly A., Russell, David H., Clemmer, David E.
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Bioinformatics; Biotechnology; Chemistry; Chemistry and Materials Science; Focus: Mass Spectrometry as a Probe of Higher Order Protein Structure: Research Article; Folding; Ionic mobility; Mass spectrometry; Organic Chemistry; Peptides - chemistry; Phase transitions; Proline; Protein Folding; Protein Structure, Secondary; Proteomics; Solvents; Thermodynamics
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1007/s13361-016-1372-6

When the all- cis polyproline-I helix (PPI, favored in 1-propanol) of polyproline-13 is introduced into water, it folds into the all- trans polyproline-II (PPII) helix through at least six intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702–12711 ( 2014 )]. Here, we show that the solvent-free intermediates refold into the all- cis PPI helix with high (>90%) efficiency. Moreover, in the absence of solvent, each intermediate appears to utilize the same small set of pathways observed for the solution-phase PPII → PPI transition upon immersion of PPII aq in 1-propanol. That folding in solution (under conditions where water is displaced by propanol) and folding in vacuo (where energy required for folding is provided by collisional activation) occur along the same pathway is remarkable. Implicit in this statement is that 1-propanol mimics a “dry” environment, similar to the gas phase. We note that intermediates with structures that are similar to PPII aq can form PPII under the most gentle activation conditions—indicating that some transitions observed in water (i.e. , “we t ” folding, are accessible (albeit inefficient) in vacuo. Lastly, these “dry” folding experiments show that PPI (all cis ) is favored under “dry” conditions, which underscores the role of water as the major factor promoting preference for trans proline. Graphical Abstract ᅟ