Structural Basis of APOBEC Functions and HIV Restriction

APOBEC 功能和 HIV 限制的结构基础

基本信息

  • 批准号:
    10647803
  • 负责人:
  • 金额:
    $ 43.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-04-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

Project Summary Structural Basis of APOBEC Functions and HIV Restriction Apolipoprotein B mRNA-editing Enzyme Catalytic polypeptide (APOBEC) family of cytidine deaminases are capable of deaminating the cytidine to cause mutation to uridine on DNA or RNA. Human APOBEC deaminases have remarkable diverse cellular functions through specific targeting to the intended ssDNA or RNA through a combination of regulations including spatial and temporal distribution and substrate specificity. For example, APOBEC1 (A1) edits certain RNAs with the help of specific cofactors to regulate cholesterol metabolism; AID has important role in acquired immune response, it is required for antibody maturation including somatic hypermutation (SHM) and class switch recombination (CSR); APOBEC2 (A2) is involved in cardiac and skeletal muscle development; and APOBEC3 proteins (A3s, A3A-H) plays an important role in innate immunity for anti-viral activity, they can restrict internal and external nucleic acids (such as RNA and DNA viruses and retroelements) that poses danger to the genome integrity, which include internal retroelements as well as external retroviruses and other infectious viral pathogens, such as Hepatitis B Virus (HBV), Human Papillomavirus (HPV), and Human Immunodeficiency Virus (HIV). Among APOBEC proteins, A3G/A3F/A3D/A3H display strong anti-HIV activity, which are through deaminase-dependent and -independent mechanisms to inhibit viral replication and infection. However, retroviruses like HIV-1 can overcome the anti-HIV activity of APOBEC enzymes by its virus virulent factor (Vif) that specifically recruit cellular Cul5 E3 ligase to target these APOBECs for ubiquitination and degradation, leading to the viral infection. The deamination activity of APOBECs can also cause accidental genomic mutations, which can lead to various human diseases such as immune deficiency and cancer. Our long-term scientific goals are to understand the structural/functional relationship for APOBEC cellular functions and their anti-viral activities. Our specific aims are to understand the structural basis of APOBEC’s functions and the mechanisms that underlie nucleic acid interactions, multimerization, functional regulation, and viral restriction, with particular focuses on the double domain APOBEC3 subfamily members that have strong anti-retroelements and anti-HIV activities. The outcome of this research will provide valuable information for the fundamental molecular mechanisms of APOBEC functions and their anti viral activities, which can be used for the potential drug development to provide therapy for HIV/AIDS, immune disorders, and other diseases such as cancer.
项目总结

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase.
  • DOI:
    10.1126/sciadv.ade3168
  • 发表时间:
    2023-01-04
  • 期刊:
  • 影响因子:
    13.6
  • 作者:
  • 通讯作者:
Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15.
SARS-CoV-2 Nsp15 识别多聚尿苷束的结构基础。
  • DOI:
    10.1101/2023.11.17.567629
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ito,Fumiaki;Yang,Hanjing;Zhou,ZHong;Chen,XiaojiangS
  • 通讯作者:
    Chen,XiaojiangS
Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G.
  • DOI:
    10.1038/s41467-022-35201-9
  • 发表时间:
    2022-12-05
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Yang, Hanjing;Kim, Kyumin;Li, Shuxing;Pacheco, Josue;Chen, Xiaojiang S.
  • 通讯作者:
    Chen, Xiaojiang S.
Insights into the Structures and Multimeric Status of APOBEC Proteins Involved in Viral Restriction and Other Cellular Functions.
  • DOI:
    10.3390/v13030497
  • 发表时间:
    2021-03-17
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Chen XS
  • 通讯作者:
    Chen XS
Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H.
  • DOI:
    10.1038/s41467-023-40955-x
  • 发表时间:
    2023-08-28
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Ito F;Alvarez-Cabrera AL;Kim K;Zhou ZH;Chen XS
  • 通讯作者:
    Chen XS
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XIAOJIANG S CHEN其他文献

XIAOJIANG S CHEN的其他文献

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{{ truncateString('XIAOJIANG S CHEN', 18)}}的其他基金

Structural Studies of MCM Complex
MCM复合体的结构研究
  • 批准号:
    8126571
  • 财政年份:
    2010
  • 资助金额:
    $ 43.8万
  • 项目类别:
Structural Basis of APOBEC Functions and HIV Restriction
APOBEC 功能和 HIV 限制的结构基础
  • 批准号:
    10436802
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Structural Basis of APOBEC Functions and Interactions with HIV-Vif
APOBEC 功能的结构基础以及与 HIV-Vif 的相互作用
  • 批准号:
    9204296
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Structural Studies of MCM Complex
MCM复合体的结构研究
  • 批准号:
    7752585
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Understanding The Structural Basis of APOBEC Functions
了解 APOBEC 功能的结构基础
  • 批准号:
    7790588
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Understanding The Structural Basis of APOBEC Functions
了解 APOBEC 功能的结构基础
  • 批准号:
    8244450
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Structural Basis of APOBEC Functions and Interactions with HIV-Vif
APOBEC 功能的结构基础以及与 HIV-Vif 的相互作用
  • 批准号:
    9537133
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Understanding The Structural Basis of APOBEC Functions
了解 APOBEC 功能的结构基础
  • 批准号:
    8053875
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Structural Studies of MCM Complex
MCM复合体的结构研究
  • 批准号:
    8204543
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
Structural Studies of MCM Complex
MCM复合体的结构研究
  • 批准号:
    8001970
  • 财政年份:
    2009
  • 资助金额:
    $ 43.8万
  • 项目类别:
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