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Not Always Sticky: Specificity of Protein Stabilization by Sugars Is Conferred by Protein-Water Hydrogen Bonds
Gil I Olgenblum1, Neta Carmon1, Daniel Harries1
1The Fritz Haber Research Center, and the Harvey M. Kruger Center for Nanoscience & Nanotechnology, Institute of Chemistry, The Hebrew University, Jerusalem 9190401, Israel.
Journal of the American Chemical Society
|October 16, 2023
Summary
Sugar interactions with proteins are protein-specific, influencing protein folding. These soft interactions can stabilize or destabilize protein structures, depending on the protein
Area of Science:
- Biochemistry
- Chemical Physics
- Molecular Biology
Background:
- Protein folding is influenced by solutes in buffered solutions.
- Protein stabilization by cosolutes typically involves volume exclusion and chemical/soft interactions.
- Previous research suggested soft protein-sugar attractions are invariably destabilizing.
Purpose of the Study:
- To investigate the protein-specific nature of soft interactions between proteins and sugar cosolutes.
- To determine if soft interactions can be stabilizing or destabilizing for protein folding.
- To elucidate the mechanisms underlying protein folding modulation by sugars and polyols.
Main Methods:
- Experimental observation of the folding of two model miniproteins in the presence of sugars and polyols.
- Application of a mean-field model to analyze protein-sugar interactions.
- Molecular dynamics simulations to investigate the impact of sugars on protein-water hydrogen bonding.
Main Results:
- Sugars and polyols induced distinct secondary structures (β-hairpin or α-helix) in marginally stable miniproteins.
- While excluded volume interactions had a similar stabilizing effect, soft interactions were protein-specific, causing stabilization in one and destabilization in another.
- Soft protein-sugar interactions weaken protein-water hydrogen bonds, with variable effects on folding free energy based on amino acid sequence.
Conclusions:
- Soft interactions between proteins and sugars are protein-specific and can be either stabilizing or destabilizing.
- The variation in soft interactions dictates the unique response of different proteins to the same sugar cosolute.
- Protein sequence is a critical determinant of how soft interactions influence folding free energy.
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