Methods for Inducing Homologous Protein Dimerization
10.16476/j.pibb.2024.0106
- VernacularTitle:诱导同源蛋白质二聚化的方法
- Author:
Jun-Xia GUO
1
;
Sen LIU
1
Author Information
1. Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), College of Life Science and Health Engineering, Hubei University of Technology, Wuhan430068, China
- Publication Type:Journal Article
- Keywords:
protein-protein interaction;
proximity induction;
homodimerization;
CID;
LID
- From:
Progress in Biochemistry and Biophysics
2024;51(11):2805-2820
- CountryChina
- Language:Chinese
-
Abstract:
Proteins in biological systems rarely act alone, but instead bind with other biomolecules to trigger specific cellular reactions. These biomolecules are usually astonishing number of proteins self-assemble to form dimers, which are both in a relatively isolated state and in a protein interaction network and cascade. Dimerization can endow proteins with various structural and functional advantages, including improving stability, controlling the accessibility and specificity of active sites, and increasing complexity. The self-association of proteins to form dimers is a very common phenomenon, and the functional importance of homologous protein dimerization cannot be overestimated. It provides diversity and specificity in many pathways, and most cellular events, such as signal transduction, transcription cofactor recruitment, enzyme activation, and even pathogenic pathways, are significantly regulated through homologous protein-protein interactions. The regulation of protein dimerization is an important process for the growth and development of organisms under internal or external stimuli in the natural environment. Therefore, regulating the dimerization process of homologous proteins and understanding their molecular mechanisms are crucial for biomedical applications and analyzing complex biological regulatory networks. Proximity effects or physical proximity effects of molecules are essential regulatory factors in biological processes, which can be controlled through induced dimerization methods. The application range of induced proximity ranges from manipulating protein folding, activation, localization, and degradation to controlling gene transcription or cell therapy. The chemical induced dimerization (CID) system and light induced dimerization (LID) system based on proximity induction provide powerful tools for regulating the function of dimerized proteins, and have been gradually developed. The concept of CID was proposed as early as 1993. The basic principle of CID is that a small molecule controls the dimerization of a pair of proteins or domains, while binding two proteins and bringing them closer together. Small molecules in the CID system form ternary complexes with target proteins, which can bind to various sites, including “hotspot” and “allosteric sites”. Small molecules play a role by regulating protein proximity. The light induced dimerization system uses photosensitive proteins to undergo conformational changes under light, thereby inducing protein interactions. Multiple photosensitive proteins derived from plants and microorganisms can undergo photo induced homologous interactions, and relying on LID systems, they can be used to study various biological processes, including cell signal transduction, microbial synthesis, and biomedical applications. In recent years, metal ions, nucleic acids, and molecular host guest systems have been proposed as new methods for orthogonal control of homologous protein dimerization, expanding the development and application of dimerization systems. In addition, the chemo-optogenetic approach combines the advantages of CID and LID systems and has also been applied in inducing protein dimerization. This review elaborates on the methods and applications of inducing homodimerization of proteins through CID system, LID system, and supramolecular chemistry, while discussing the advantages and disadvantages of dimerization systems. The development direction of dimerization systems is also discussed, in order to provide some reference and ideas for the future application and development of homologous protein dimerization.
