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
- 来源:
- 关键词:3-DimensionalAPOBEC2 geneAccidentsAddressAffinityAnti-HIV AgentsAntibodiesBindingBiologicalBiological ProcessBiologyC-terminalCardiacCell physiologyCholesterolCholesterol HomeostasisComplementary DNAComplexCryoelectron MicroscopyCullin 5 ProteinCytidineCytidine DeaminaseCytosine deaminaseDNADNA VirusesDeaminaseDeaminationDiseaseEnzymesFamilyGenerationsGenome StabilityGenomic InstabilityGenomicsGoalsHIVHIV InfectionsHIV therapyHIV-1HIV/AIDSHepatitis B VirusHumanHuman GenomeHuman PapillomavirusHyperimmunoglobulin M SyndromeImmuneImmune System DiseasesImmune responseImmunityImmunoglobulin Class SwitchingImmunoglobulin Somatic HypermutationImmunoglobulin Switch RecombinationInfectionLengthMalignant NeoplasmsMediatingMessenger RNAMolecularMuscle DevelopmentMutationMyocardiumN-terminalNatural ImmunityNucleic AcidsOutcomes ResearchPlayProteinsRNARNA BindingRNA VirusesRNA-Directed DNA PolymeraseRegulationResearchRetroelementsRetrotranspositionRetroviridaeReverse TranscriptionRiskRoentgen RaysRoleSingle-Stranded DNASkeletal MuscleSpecificityStructureSubstrate SpecificityUbiquitinationUridineViralViral PhysiologyVirionVirulentVirusVirus DiseasesVirus Replicationantiviral immunityapoB mRNA editing catalytic subunitapolipoprotein B mRNA editing enzymecofactordrug developmenteffective therapyelongin Bgenome integrityhuman diseasemembermulticatalytic endopeptidase complexnovelpathogenic viruspolypeptidepreventrecruitubiquitin-protein ligaseviral genomics
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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{{ truncateString('XIAOJIANG S CHEN', 18)}}的其他基金
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:
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: