Contribution of Electrostatic Interactions, Compactness and Quaternary Structure to Protein Thermostability: Lessons from Structural Genomics of Thermotoga maritima

Abstract

Studies of the structural basis of protein thermostability have produced a confusing picture. Small sets of proteins have been analyzed from a variety of thermophilic species, suggesting different structural features as responsible for protein thermostability. Taking advantage of the recent advances in structural genomics, we have compiled a relatively large protein structure dataset, which was constructed very carefully and selectively; that is, the dataset contains only experimentally determined structures of proteins from one specific organism, the hyperthermophilic bacterium Thermotoga maritima, and those of close homologs from mesophilic bacteria. In contrast to the conclusions of previous studies, our analyses show that oligomerization order, hydrogen bonds, and secondary structure play minor roles in adaptation to hyperthermophily in bacteria. On the other hand, the data exhibit very significant increases in the density of salt-bridges and in compactness for proteins from T.maritima. The latter effect can be measured by contact order or solvent accessibility, and network analysis shows a specific increase in highly connected residues in this thermophile. These features account for changes in 96% of the protein pairs studied. Our results provide a clear picture of protein thermostability in one species, and a framework for future studies of thermal adaptation.

Structure, Function, and Targets of the Transcriptional Regulator SvtR from the Hyperthermophilic Archaeal Virus SIRV1

“…The same limitations apply to the apparent affinities (IC 50,u ) of SvtR to its cognate DNAs. However, we speculate that the network of inter-monomer salt bridges (69,70), together with the compact network of intermolecular hydrophobic interactions might be important in stabilizing the dimer at higher temperatures. If this were not the case, the monomerdimer equilibrium could play a role as a switch between inactive (monomer) and active (dimer) conformations.…”

Defining the Role of Salt Bridges in Protein Stability

“…Recently, an increasing number of observations strengthens the view, that electrostatic interactions are an important factor conferring thermostability to proteins, although opposite views also exist (89)(90)(91)(92)(93)(94). The overall trend of an increased number of salt bridges in proteins from organisms with higher optimal growth temperature is illustrated in Fig.…”

Distinct Roles for Carbohydrate-Binding Modules of Glycoside Hydrolase 10 (GH10) and GH11 Xylanases from Caldicellulosiruptor sp. Strain F32 in Thermostability and Catalytic Efficiency

“…The effects of various sequence and structural determinants of thermophilic adaptation have been investigated (13,14). Usually, thermophilic adaptation of proteins involves optimized packing of hydrophobic interactions and increased density of salt-bridge or charge-assisted hydrogen bonds.…”

“…Usually, thermophilic adaptation of proteins involves optimized packing of hydrophobic interactions and increased density of salt-bridge or charge-assisted hydrogen bonds. In many cases, a combination of the structural features described above is crucial to achieve increased thermostability (14)(15)(16). These structural changes contribute to the protein thermophilic adaptation of the potential network of noncovalent interaction within the protein, presumably leading to a balance between overall rigidity, which is important for thermostability, and local flexibility, which is important for activity (17).…”