Structure based analysis of human herpesvirus 6 transactivator IE2

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15075
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kobe University
• Principal Investigator: Nishimura Mitsuhiro 神戸大学, 医学研究科, 助教 (40510285)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ヒトヘルペスウイルス6 / X線結晶構造解析

Outline of Final Research Achievements

研究成果の概要（英文）：
Human herpesvirus 6 infects almost all humans during infancy, although the infection mechanism and pathogenicity still remain unclear. A HHV-6 viral protein, immediate early protein 2 (IE2), expresses immediately after the infection and promote the expression of the other viral factors as a transactivator. In this study, the structure and function of IE2 protein were analyzed. A DNA binding-model of IE2 C-terminal domain (IE2-CTD) was constructed based on the determined structure. Putative functional sites of IE2-CTD were proposed from the structural analysis, and several sites were proved to be significant on the IE2 transactivation function by a mutation analysis.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究ではヒトヘルペスウイルス6の感染開始時に重要な働きを持つIE2についてそのC末端領域の立体構造を詳細に解析し、IE2の転写活性化機能に必要な機能部位を新たに見出すことができた。これらの成果はHHV-6の感染において、実際にIE2がウイルスタンパク質としてどのように機能するかをその立体構造に基づいて解析したものであり、さらに今後IE2がヒト細胞内の宿主因子とどのように相互作用するかを解析していくための手掛かりとなることで、ウイルス感染機構の解明及びその制御法開発へ繋がる事が期待できる。