Elucidation of physical properties and intracellular functions of unanchored atypical ubiquitin chains

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15757
• 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: Morimoto Daichi 京都大学, 工学研究科, 助教 (40746616)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ユビキチン / 構造ゆらぎ / ATP / 環状 / NMR

Outline of Final Research Achievements

Conjugation of ubiquitin chains with substrates plays a role in various biological phenomena. Recently, atypical (branched and cyclic chains) and unanchored ubiquitin chains have been identified. However, their physical properties and functions remain poorly understood. In this study, we conducted a structural analysis of atypical and unanchored ubiquitin chains using solution NMR to gain a deeper understanding of their characteristics. Our findings reveal that ubiquitin chains exhibit distinct structural fluctuations among ubiquitin units, which are related with susceptibility of post-translational modifications. In addition, ubiquitin weakly interacts with ATP, which is abundantly present in cells. This suggests that ubiquitin chains are less likely to self-associate or aggregate in cells. Additionally, cyclic ubiquitin chains demonstrate a different recognition mechanism compared with the noncyclic form and the cyclic chains are found to be less prone to cleavage.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

これまでのユビキチン鎖研究は単一の結合型で形成された直鎖状の短いユビキチン鎖が中心であった。だが現在、続々と非定型のユビキチン鎖が発見されており、ユビキチン鎖研究でパラダイムシフトが起こっている状況にある。本研究で明らかにしたユビキチン鎖におけるユニット間の異なる構造ゆらぎ、ATPとの弱い相互作用、環状鎖の特異的な認識機構はいずれも既存のユビキチンバイオロジーでは想定できなかった知見であり、新規の概念を与えるものとなった。また、タンパク質科学の観点から、これまでの静的な構造解析とは一線を画し、タンパク質機能を明らかにする上での動的構造解析の重要性を示した研究結果となった。