Competitive linear ubiquitin binding in NFkB-signaling

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15756
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Kyoto University
• Principal Investigator: WALINDA Erik 京都大学, 医学研究科, 助教 (80782391)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ubiquitin / ubiquitin binding / NZF domain / M1 ubiquitin chains / linear ubiquitin chains / NMR spectroscopy / ITC / MD simulations

Outline of Final Research Achievements

In these two yearsl our research has proceeded rather smoothly. We were able to publish several aspects of this project in various international peer-reviewed journals.

The project focuses on protein ubiquitylation, attaching ubiquitin to target proteins. Initially, it studied K48-linked polyubiquitin chains for degradation. The discovery of linear ubiquitin chains and LUBAC's role in immune signaling necessitated understanding them further. The study aims to explore HOIL-1L's binding specificity to linear ubiquitin chains, conformational changes, preference for M1-linked polyubiquitin, and its role in HOIL-1L and LUBAC. Key findings include optimized purification of LUBAC fragments for cancer drug screening, investigating cyclization's impact on ubiquitin chain recognition by OTUB1, and examining linear ubiquitin recognition by HOIL-1L NZF domain. These results enhance understanding of linear ubiquitin binding and the ubiquitin code.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

Scientific significance: understanding non-proteolytic functions of ubiquitin chains, particularly in immune signaling, survival, inflammation, immune disorders, cancer, and infectious diseases.

Social significance: potential to contribute to the development of treatments for immune disorders.