Salt bridges, protein stability

The association of two oppositely charged ionic groups in a protein is known as a salt bridge or ion pair and is a common feature of most proteins. Typically these interactions contribute very little to protein stability since the isolated ionic groups are so effectively solvated by water. As a consequence very few unsolvated salt bridges are found in the interior of proteins. Furthermore, salt bridges are rarely conserved in orthologous proteins. 

Two different models have been proposed to explain how regulatory phosphorylation sites may exert their function. Either the dianionic phosphoserine is salt-linked to an arginine or lysine residue and in doing so may help stabilize one spedfic protein conformation, or a mobile phosphoryl group may prevent an interaction between protein domains. In the latter case, one would expect the resonance to show titration behavior with a Hill coefficient similar to that of standards, which is indeed observed for some of the proteins. When salt bridges play a role, the energy involved has to be <5 kcal mol in order to observe a titration behavior. A lower pA, and an increased Hill coeffident (n > 1) can provide evidence for the presence of proximal positive charges. 

Also important for stabilizing a protein s tertiary stmcture are the formation of disulfide bridges between cysteine residues, the formation of hydrogen bonds between nearby amino acid residues, and the presence of ionic attractions, called salt bridges, between positively and negatively charged sites on various amino acid side chains within the protein. 

While loops lack apparent stmcmral regularity, they exist in a specific conformation stabilized through hydrogen bonding, salt bridges, and hydrophobic interactions with other portions of the protein. However, not all portions of proteins are necessarily ordered. Proteins may contain disordered regions, often at the extreme amino or carboxyl terminal, characterized by high conformational flexibility. In many instances, these disor-... 

Bosshard, H.R., Marti, D.N., and Jelesarov, I. 2004. Protein stabilization by salt bridges concepts, experimental approaches and clarification of some misunderstandings. Journal of Molecular Recognition 17(1), 1-16. 

Cytochrome c and cytochrome c peroxidase (ccp) are physiological partners in the ccp reaction cycle structural, thermodynamic, and kinetic data are available for the protein-protein interaction [69-72]. A model indicates that the cyt c/ccp complex is stabilized by specific salt bridges with the hemes in parallel planes the Fe-Fe distance is 24 A, and the edge-edge distance is 16 A [70]. 

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