Preferential Water Exclusion in Protein Unfolding

Association of water with protein plays a central role in the latter’s folding, structure acquisition, ligand binding, catalytic reactivity, oligomerization, and crystallization. Because these phenomena are also influenced by the net charge content on the protein, the present study examines the asso...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2014-01, Vol.118 (3), p.717-723
Main Authors: Sashi, Pulikallu, Yasin, U. Mahammad, Balasubramanian, Harihar, Sree, M. Usha, Ramakrishna, Dasari, Bhuyan, Abani K
Format: Article
Language:English
Subjects:
Alcohols
Binding
Catalysts
Charge
Correlation
Cytochromes
Cytochromes c - chemistry
Enzyme Stability
Hydrogen-Ion Concentration
Ionization
Kinetics
Protein Conformation
Protein Unfolding
Proteins
Water - chemistry
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Summary:Association of water with protein plays a central role in the latter’s folding, structure acquisition, ligand binding, catalytic reactivity, oligomerization, and crystallization. Because these phenomena are also influenced by the net charge content on the protein, the present study examines the association of water with cytochrome c held at different pH values so as to allow its side chains to ionize to variable extents. Equilibrium unfolding of differently charged cytochrome c molecules in water–methanol binary mixtures, where the alcohol acts as the cosolvent denaturant, was used to quantify the preferential exclusion of water during the unfolding transition. The extent of exclusion was found to be related to the net-charge-dependent molecular expansion of the protein in an alcohol-free aqueous medium. The degree of water exclusion was also found to be linearly related to the observed rate of protein unfolding, where the net charge contents of the initial and final states are the same. The results suggest that side-chain ionization, molecular expansion due to charge repulsion, and hence the loss of tertiary contacts lead to additional water–protein association. Protein unfolding rates appear to be linearly correlated with the effective number of water molecules excluded across the end states of unfolding equilibria.
ISSN:1520-6106
1520-5207
DOI:10.1021/jp4111103