TY - JOUR
T1 - Evolutionary Stability of Salt Bridges Hints Its Contribution to Stability of Proteins
AU - Ban, Xiaofeng
AU - Lahiri, Pratik
AU - Dhoble, Abhishek S.
AU - Li, Dan
AU - Gu, Zhengbiao
AU - Li, Caiming
AU - Cheng, Li
AU - Hong, Yan
AU - Li, Zhaofeng
AU - Kaustubh, Bhalerao
N1 - Funding Information:
This work was financially supported by the National Natural Science Foundation of China (No. 31722040 , 31771935 ), China Postdoctoral Science Foundation (No. 2018 M632233 ), the Natural Science Foundation of Jiangsu Province ( BK20180606 ), the Fundamental Research Funds for the Central Universities ( JUSRP51617B ), National First-class Discipline Program of Food Science and Technology ( JUFSTR20180204 ), the Jiangsu province “Collaborative Innovation Center of Food Safety and Quality Control” industry development program, and Qing Lan Project.
Publisher Copyright:
© 2019 The Authors
PY - 2019
Y1 - 2019
N2 - The contribution of newly designed salt bridges to protein stabilization remains controversial even today. In order to solve this problem, we investigated salt bridges from two aspects: spatial distribution and evolutionary characteristics of salt bridges. Firstly, we analyzed spatial distribution of salt bridges in proteins, elucidating the basic requirements of forming salt bridges. Then, from an evolutionary point of view, the evolutionary characteristics of salt bridges as well as their neighboring residues were investigated in our study. The results demonstrate that charged residues appear more frequently than other neutral residues at certain positions of sequence even under evolutionary pressure, which are able to form electrostatic interactions that could increase the evolutionary stability of corresponding amino acid regions, enhancing their importance to stability of proteins. As a corollary, we conjectured that the newly designed salt bridges with more contribution to proteins, not only, are qualified spatial distribution of salt bridges, but also, are needed to further increase the evolutionary stability of corresponding amino acid regions. Based on analysis, the 8 mutations were accordingly constructed in the 1,4-α-glucan branching enzyme (EC 2.4.1.18, GBE) from Geobacillus thermoglucosidans STB02, of which 7 mutations improved thermostability of GBE. The enhanced thermostability of 7 mutations might be a result of additional salt bridges on residue positions that at least one of amino acids positions is conservative, improving their contribution of stabilization to proteins.
AB - The contribution of newly designed salt bridges to protein stabilization remains controversial even today. In order to solve this problem, we investigated salt bridges from two aspects: spatial distribution and evolutionary characteristics of salt bridges. Firstly, we analyzed spatial distribution of salt bridges in proteins, elucidating the basic requirements of forming salt bridges. Then, from an evolutionary point of view, the evolutionary characteristics of salt bridges as well as their neighboring residues were investigated in our study. The results demonstrate that charged residues appear more frequently than other neutral residues at certain positions of sequence even under evolutionary pressure, which are able to form electrostatic interactions that could increase the evolutionary stability of corresponding amino acid regions, enhancing their importance to stability of proteins. As a corollary, we conjectured that the newly designed salt bridges with more contribution to proteins, not only, are qualified spatial distribution of salt bridges, but also, are needed to further increase the evolutionary stability of corresponding amino acid regions. Based on analysis, the 8 mutations were accordingly constructed in the 1,4-α-glucan branching enzyme (EC 2.4.1.18, GBE) from Geobacillus thermoglucosidans STB02, of which 7 mutations improved thermostability of GBE. The enhanced thermostability of 7 mutations might be a result of additional salt bridges on residue positions that at least one of amino acids positions is conservative, improving their contribution of stabilization to proteins.
KW - Evolutionary stability
KW - Evolutionary trace
KW - Mutagenesis
KW - Salt bridge
KW - Thermostability
UR - http://www.scopus.com/inward/record.url?scp=85068523778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068523778&partnerID=8YFLogxK
U2 - 10.1016/j.csbj.2019.06.022
DO - 10.1016/j.csbj.2019.06.022
M3 - Article
AN - SCOPUS:85068523778
SN - 2001-0370
VL - 17
SP - 895
EP - 903
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
ER -