Robic Srebrenka, Guzman-Casado Mercedes, Sanchez-Ruiz Jose M, Marqusee Susan
Department of Molecular and Cell Biology, QB3 Institute, 215 Hildebrand Hall mc 3206, University of California, Berkeley, CA 94720-3206, USA.
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11345-9. doi: 10.1073/pnas.1635051100. Epub 2003 Sep 22.
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.
嗜热细菌嗜热栖热菌和嗜温菌大肠杆菌的核糖核酸酶H在展开时的热容变化（ΔCp°）表现出显著且惊人的差异。嗜热蛋白较低的ΔCp°直接导致其较高的热变性温度（Tm）。我们提出，这种ΔCp°差异源于嗜热蛋白未折叠状态下的残余结构；我们通过诱变方法验证了这一假设。未折叠状态下的残余结构可能为平衡高Tm与蛋白质功能的最佳热力学稳定性提供一种机制。结果表明，未折叠状态下的结构对嗜热蛋白和嗜温蛋白的热力学概况有不同影响。
