Do guanidinium and tetrapropylammonium ions specifically interact with aromatic amino acid side chains?
- aDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104;
- bUltrafast Optical Processes Laboratory, University of Pennsylvania, Philadelphia, PA 19104
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Edited by Michael L. Klein, Temple University, Philadelphia, PA, and approved December 16, 2016 (received for review November 1, 2016)
Significance
Ever since the discovery by Franz Hofmeister in 1888 that a series of salts (now commonly referred to as the Hofmeister series) can have different but consistent effects on the solubility and hence stability of proteins, many studies have been devoted to understanding how such effects are achieved. However, examining any specific mode of ion–protein interactions has proven to be difficult. Herein, we demonstrate, using guanidinium and tetrapropylammonium as examples, that it is possible to use multiple spectroscopic methods and unnatural amino acids that have distinct, environment-sensitive fluorescence and infrared properties to explicitly assess how these ions interact with a specific type of amino acid side chains, thus yielding microscopic insights into their protein-denaturing mechanisms.
Abstract
Many ions are known to affect the activity, stability, and structural integrity of proteins. Although this effect can be generally attributed to ion-induced changes in forces that govern protein folding, delineating the underlying mechanism of action still remains challenging because it requires assessment of all relevant interactions, such as ion–protein, ion–water, and ion–ion interactions. Herein, we use two unnatural aromatic amino acids and several spectroscopic techniques to examine whether guanidinium chloride, one of the most commonly used protein denaturants, and tetrapropylammonium chloride can specifically interact with aromatic side chains. Our results show that tetrapropylammonium, but not guanidinium, can preferentially accumulate around aromatic residues and that tetrapropylammonium undergoes a transition at ∼1.3 M to form aggregates. We find that similar to ionic micelles, on one hand, such aggregates can disrupt native hydrophobic interactions, and on the other hand, they can promote α-helix formation in certain peptides.
Footnotes
- ↵1To whom correspondence should be addressed. Email: gai{at}sas.upenn.edu.
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Author contributions: B.D. and F.G. designed research; B.D., D.M., and J.C. performed research; B.D. analyzed data; and B.D., D.M., and F.G. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1618071114/-/DCSupplemental.
