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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Role of residual structure in the unfolded state of a thermophilic protein
Srebrenka Robic1, Mercedes Guzman-Casado, Jose M Sanchez-Ruiz
1Department of Molecular and Cell Biology, QB3 Institute, 215 Hildebrand Hall mc 3206, University of California, Berkeley, CA 94720-3206, USA.
Abstract:
Ribonucleases H from the thermophilic bacterium Thermus thermophilus and the mesophile Escherichia coli demonstrate a dramatic and surprising difference in their change in heat capacity upon unfolding (DeltaCp degrees ). The lower DeltaCp degrees of the thermophilic protein directly contributes to its higher thermal denaturation temperature (Tm). We propose that this DeltaCp degrees difference originates from residual structure in the unfolded state of the thermophilic protein; we verify this hypothesis by using a mutagenic approach. Residual structure in the unfolded state may provide a mechanism for balancing a high Tm with the optimal thermodynamic stability for a protein's function. Structure in the unfolded state is shown to differentially affect the thermodynamic profiles of thermophilic and mesophilic proteins.
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