Structural adaptation of the subunit interface of oligomeric thermophilic and hyperthermophilic enzymes.
Enzymes from thermophilic and, particularly, from hyperthermophilic organisms are surprisingly stable. Understanding of the molecular origin of protein thermostability and thermoactivity attracted the interest of many scientist both for the perspective comprehension of the principles of protein structure and for the possible biotechnological applications through application of protein engineering. Comparative studies at sequence and structure levels were aimed at detecting significant differences of structural parameters related to protein stability between thermophilic and hyperhermophilic structures and their mesophilic homologs. Comparative studies were useful in the identification of a few recurrent themes which the evolution utilized in different combinations in different protein families. These studies were mostly carried out at the monomer level. However, maintenance of a proper quaternary structure is an essential prerequisite for a functional macromolecule. At the environmental temperatures experienced typically by hyper- and thermophiles, the subunit interactions mediated by the interface must be sufficiently stable. Our analysis was therefore aimed at the identification of the molecular strategies adopted by evolution to enhance interface thermostability of oligomeric enzymes. The variation of several structural properties related to protein stability were tested at the subunit interfaces of thermophilic and hyperthermophilic oligomers. The differences of the interface structural features observed between the hyperthermophilic and thermophilic enzymes were compared with the differences of the same properties calculated from pairwise comparisons of oligomeric mesophilic proteins contained in a reference dataset. The significance of the observed differences of structural properties was measured by a t-test. Ion pairs and hydrogen bonds do not vary significantly while hydrophobic contact area increases specially in hyperthermophilic interfaces. Interface compactness also appears to increase in the hyperthermophilic proteins. Variations of amino acid composition at the interfaces reflects the variation of the interface properties.
Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università degli Studi di Roma "La Sapienza", Rome, Italy.
Elisa
E
Maugini
Daniele
D
Tronelli
Francesco
F
Bossa
Stefano
S
Pascarella
D018360:Crystallography, X-Ray; D030562:Databases, Protein; D004798:Enzymes / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature
D004798:Enzymes; D021122:Protein Subunits; D011506:Proteins