Molecular dynamics simulation of force-regulated interaction between talin and Rap1b.
10.7507/1001-5515.202208022
- Author:
Zhe YU
1
;
Yanru JI
1
;
Wenhua HUANG
2
;
Ying FANG
1
;
Jianhua WU
1
Author Information
1. School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, P. R. China.
2. National Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical University, Guangdong Provincial Key Laboratory of Medical Biomechanics, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangzhou 510515, P. R. China.
- Publication Type:Journal Article
- Keywords:
Biphasic force-dependent;
Molecular dynamics simulation;
Rap1b;
Talin-1
- MeSH:
Molecular Dynamics Simulation;
Talin
- From:
Journal of Biomedical Engineering
2023;40(4):645-653
- CountryChina
- Language:Chinese
-
Abstract:
The binding of talin-F0 domain to ras-related protein 1b (Rap1b) plays an important role in the formation of thrombosis. However, since talin is a force-sensitive protein, it remains unclear whether and how force regulates the talin-F0/Rap1b interaction. To explore the effect of force on the binding affinity and the dynamics mechanisms of talin-F0/Rap1b, molecular dynamics simulation was used to observe and compare the changes in functional and conformational information of the complex under different forces. Our results showed that when the complex was subjected to tensile forces, there were at least two dissociation pathways with significantly different mechanical strengths. The key event determining the mechanical strength difference between the two pathways was whether the β4 sheet of the F0 domain was pulled away from the original β1-β4 parallel structure. As the force increased, the talin-F0/Rap1b interaction first strengthened and then weakened, exhibiting the signature of a transition from catch bonds to slip bonds. The mechanical load of 20 pN increased the interaction index of two residue pairs, ASP 54-ARG 41 and GLN 18-THR 65, which resulted in a significant increase in the affinity of the complex. This study predicts the regulatory mechanism of the talin-F0/Rap1b interaction by forces in the intracellular environment and provides novel ideas for the treatment of related diseases and drug development.
