In vivo formation and new design of protein oligomers based on 3D domain swapping

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02088
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Hirota Shun 奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (90283457)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: タンパク質 / 3Dドメインスワッピング / 金属タンパク質 / 多量化 / タンパク質デザイン

Outline of Final Research Achievements

3D domain swapping is a phenomenon in which the same protein molecule exchanges the same structural region between molecules. Domain swapping was first reported in 1994. In recent years, there has been an increase in knowledge about the structure of domain-swapped proteins, but the mechanism and conditions under which domain swapping occurs in vivo have not been elucidated. In addition, oligomerization of proteins is useful for enhancing their structures and functions. However, it is difficult to artificially construct a protein nanostructure, and a general method has not been established yet. In this study, the mechanism and conditions of in vivo domain swapping are investigated. Protein oligomers with unique structures are constructed based on domain swapping.

Free Research Field

生体関連化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、生体内でタンパク質多量化機構を分子レベルで解明し、機能性タンパク質多量体の創製を行う、新しい試みである。アンフィンセンのドグマではタンパク質はアミノ酸配列が決まれば、その立体構造が一意的に決まるとされているが、生体内でタンパク質は3Dドメインスワッピングし、必ずしも立体構造が一意的に決まらない。そのため、生体内でタンパク質がドメインスワッピングする機構や条件を解明することは重要である。また、タンパク質高次構造体形成の制御方法を開発することは、生体適合性に優れた物質輸送技術の創出に繋がる。