Study on molecular and structural basis of anti-retroviral activity by APOBEC3

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: IWATANI YASUMASA 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (90303403)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ウイルス / 生体分子 / 酵素 / タンパク質 / 生体防御因子

Outline of Final Research Achievements

Human APOBEC3 family proteins are powerful cellular defense factors that potently inhibit replication of retroviruses, including HIV and retrotransposons. However, some retroviruses such as HIV replicate by expressing Vif protein, which specifically eliminates the APOBEC3s' antiviral functions. In this research project, we obtained two major findings: 1) the antiviral molecular mechanisms are fundamentally linked to their homo-oligomerization capacity, which is directly correlated with affinity (dissociation constants) to single-stranded nucleic acids; 2) the Vif-binding conformations on APOBEC3C/F/D are characterized as shallow hydrophobic cavities surrounded with negatively-charged area. These data provide important and novel information to further understand the molecular mechanisms of APOBEC3s' antiviral functions.

Free Research Field

医歯薬学