Structural adaptation of enzymes from halophilic organisms

Proteins from halophilic organisms, especially those who adopt ‘salt in’ survival strategy, i.e. accumulation of inorganic ions up to 5 M in the cytoplasm, maintain their soluble and active conformations, in an environment generally detrimental to proteins. Indeed, hypersaline conditions favor protein aggregation and collapse, interfere with the electrostatic interactions between protein residues, and are responsible for a general decrease in the availability of water molecules. Halophilic proteins, rather than being denaturated by these conditions, appear to be dependent on the presence of salts. In recent years, detailed investigations have been carried out to unveil the relationship between structure and stability in halophilic proteins. In particular, it was observed that halophilic proteins are characterized by a general increase in solvent-accessible acidic amino acids content, a general decrease in hydrophobic amino acids and a greater propensity to form random-coil structures, rather than -helices. Moreover, protein folding and adequate stability of the native structure in a hypersaline environment may require evolutionary adjustments in the hydrophobic interactions within the hydrophobic nucleus. In the present work indeed we report a systematic comparison between the available three dimensional structure of halophilic enzymes and the structure of one of their homologues, to investigate the differences in terms of structural adaptation to high salt environments with particular attention to the conserved hydrophobic contacts. In the present work a structural comparison between halophilic proteins and their non-halophilic counterparts was carried out. Several structural characteristics were taken into account: the solvent accessible surface area, the surface electrostatic potential and the apolar contact area, calculated between equivalent structurally and evolutionarily conserved residues in halophilic and mesophilic proteins, and between the entire nucleus of the protein. Preliminary results suggest that the polar component of the solvent accessible surface area and the number of oxygen atoms exposed to solvent are greater in the halophilic enzymes, and this is reflected in the surface electrostatic potential, which is on average more electronegative. The apolar contact area between residues of the protein core and those found at the interface between different subunits is on average smaller in halophilic proteins, and the difference is even greater in the contacts formed by structurally and evolutionarily conserved residues, likely to be important in protein folding.