Impacts of the charged residues mutation S48E/N62H on the thermostability and unfolding behavior of cold shock protein: insights from molecular dynamics simulation with Gō model

• Published in: Journal of molecular modeling Vol. 22; no. 4; p. 91
• Main Authors: Su, Ji-Guo, Han, Xiao-Ming, Zhao, Shu-Xin, Hou, Yan-Xue, Li, Xing-Yuan, Qi, Li-Sheng, Wang, Ji-Hua
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Bacillus - chemistry; Bacillus - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Heat-Shock Proteins - chemistry; Heat-Shock Proteins - genetics; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Kinetics; Molecular Dynamics Simulation; Molecular Medicine; Mutation; Original Paper; Protein Domains; Protein Stability; Protein Structure, Secondary; Protein Unfolding; Species Specificity; Static Electricity; Theoretical and Computational Chemistry; Thermotoga maritima - chemistry; Thermotoga maritima - metabolism; Langevin dynamics simulation; Electrostatic interactions; Thermophilic protein; Folding/unfolding; Coarse-grained model
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-016-2958-4

The cold shock protein from the hyperthermophile Thermotoga maritima (Tm-Csp) exhibits significantly higher thermostability than its homologue from the thermophile Bacillus caldolyticus (Bc-Csp). Experimental studies have shown that the electrostatic interactions unique to Tm-Csp are responsible for improving its thermostability. In the present work, the favorable charged residues in Tm-Csp were grafted into Bc-Csp by a double point mutation of S48E/N62H, and the impacts of the mutation on the thermostability and unfolding/folding behavior of Bc-Csp were then investigated by using a modified Gō model, in which the electrostatic interactions between charged residues were considered in the model. Our simulation results show that this Tm-Csp-like charged residue mutation can effectively improve the thermostability of Bc-Csp without changing its two-state folding mechanism. Besides that, we also studied the unfolding kinetics and unfolding/folding pathway of the wild-type Bc-Csp and its mutant. It is found that this charged residue mutation obviously enhanced the stability of the C-terminal region of Bc-Csp, which decreases the unfolding rate and changes the unfolding/folding pathway of the protein. Our studies indicate that the thermostability, unfolding kinetics and unfolding/folding pathway of Bc-Csp can be artificially changed by introducing Tm-Csp-like favorable electrostatic interactions into Bc-Csp. Graphical abstract Tertiary structure of wild-type cold shock protein from the thermophile Bacillus caldolyticus