On the Molecular Basis of the Hypersaline Adaptation of Halophilic Proteins

Halophilic organisms have adapted to survive in environments with extremely high salinity, such as saline lakes. To achieve this, they modify their proteome to withstand salt concentrations that inactivate non-adapted mesophilic proteins. The surfaces of halophilic proteins feature a very characteristic amino acid composition, favoring short, polar, and acidic amino acids-such as aspartate, glutamate, and threonine-while disfavoring bulky, hydrophobic amino acids-such as lysine, methionine, and leucine. In this work, we review our understanding of the molecular basis of haloadaptation. We critically examine the role of electrostatic interactions in stabilizing halophilic proteins, while underlining the importance of other contributions from hydrophobic solvation and preferential ion exclusion. Finally, we describe the mechanistic link by which the halophilic amino acid composition optimizes function in hypersaline environments, balancing the trade-off between stability, solubility, and catalytic function.