Atomistic mechanism of the oligomerization of p53 protein in DNA scanning

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23721
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: TRAN PHUOC DUY 東京工業大学, 生命理工学院, 助教 (50848546)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: a/dPaCS-MD / p53 / IDP / docking / koff

Outline of Final Research Achievements

We developed the method to investigate the association and dissociation pathway of intrinsically disordered region of protein (IDR) to the targeted protein, and apply this method to p53 target. We find the detailed atomic mechanism of association and dissociation pathway through multiple states in which the IDR first perform the conformational selection to find the correct binding pocket following by the induced fitting mechanism to enter the correct native bound conformation. In the final state, the dehydration of the binding interfaces and secondary structure formation greatly contribute to the formation of the native bound structure. In addition, our recently developed method has ability to estimate the residence time in agreement with experimental data.

Free Research Field

生物物理

Academic Significance and Societal Importance of the Research Achievements

This research results provide detailed atomic structures of TAD-p53 bound to MDM2 which can potentially treat as drug target to help to prevent the p53 related diseases such as cancer and neurodegenerative diseases.