3 years ago

Role of Urea–Aromatic Stacking Interactions in Stabilizing the Aromatic Residues of the Protein in Urea-Induced Denatured State

Role of Urea–Aromatic Stacking Interactions in Stabilizing the Aromatic Residues of the Protein in Urea-Induced Denatured State
Aditya Chattopadhyay, U. Deva Priyakumar, Koushik Kasavajhala, Siddharth Goyal
A delicate balance of different types of intramolecular interactions makes the folded states of proteins marginally more stable than the unfolded states. Experiments use thermal, chemical, or mechanical stress to perturb the folding equilibrium for examining protein stability and the protein folding process. Elucidation of the mechanism by which chemical denaturants unfold proteins is crucial; this study explores the nature of urea–aromatic interactions relevant in urea-assisted protein denaturation. Free energy profiles corresponding to the unfolding of Trp-cage miniprotein in the presence and absence of urea at three different temperatures demonstrate the distortion of the hydrophobic core to be a crucial step. Exposure of the Trp6 residue to the solvent is found to be favored in the presence of urea. Previous experiments showed that urea has a high affinity for aromatic groups of proteins. We show here that this is due to the remarkable ability of urea to form stacking and NH−π interactions with aromatic groups of proteins. Urea–nucleobase stacking interactions have been shown to be crucial in urea-assisted RNA unfolding. Examination of these interactions using microsecond-long unrestrained simulations shows that urea–aromatic stacking interactions are stabilizing and long lasting. Further MD simulations, thermodynamic integration, and quantum mechanical calculations on aromatic model systems reveal that such interactions are possible for all the aromatic amino acid side-chains. Finally, we validate the ubiquitous nature of urea–aromatic stacking interactions by analyzing experimental structures of urea transporters and proteins crystallized in the presence of urea or urea derivatives.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b05463

DOI: 10.1021/jacs.7b05463

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.