Biophysical and structural analysis of the herpesviral nuclear budding machinery
疱疹病毒核出芽机制的生物物理和结构分析
基本信息
- 批准号:10415170
- 负责人:
- 金额:$ 59.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-05 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimalsAntiviral AgentsBindingBiochemistryBiologicalBiological ModelsBiologyBiophysicsBlindnessCapsidCapsid ProteinsCell NucleusCellsChemicalsComplexCryoelectron MicroscopyCytoplasmDataDissectionElectron Spin Resonance SpectroscopyElectrostaticsEncephalitisGoalsHerpes LabialisHerpesviridaeHumanImmunocompromised HostIn VitroIndividualInfectionIowaKnowledgeLeadLifeLipidsMalignant NeoplasmsMediatingMembraneMembrane ProteinsModelingNatureNewborn InfantNuclearNuclear EnvelopeNuclear Inner MembraneNuclear Outer MembraneNucleocapsidPhenotypePhosphorylationPopulationPositioning AttributeProcessProteinsRegulationResearchRoleScaffolding ProteinStructureSuppressor MutationsSystemTherapeutic InterventionVertebrate VirusesVesicleViralViral ProteinsVirionVirusVirus ReplicationWorkbasebiophysical techniquesburden of illnesscombatdesigndriving forceds-DNAgenital herpesin vitro Modelinnovationinterdisciplinary approachlatent infectionmutantnew therapeutic targetnovelnovel strategiesnovel therapeutic interventionparticlepathogenstructural biologyvirus envelope
项目摘要
PROJECT SUMMARY/ABSTRACT
Herpesviruses are double-stranded-DNA enveloped viruses that are among the most complex viruses infecting
animals. This proposal focuses on nuclear egress, a critical, conserved step in the assembly and release of
progeny virions during which nucleocapsids are translocated from the nucleus into the cytoplasm where they
mature into infectious virions. The viral nuclear egress complex (NEC) is the key player in this process. Using
in vitro model systems, we previously discovered that the NEC is a complete, virally encoded membrane
budding machine that operates at the nuclear envelope. However, a major barrier to understanding nuclear
egress is the lack of knowledge of how the NEC generates membrane curvature that results in budding. The
long-term goal of this research is to elucidate the detailed mechanism of herpesvirus nuclear egress, both to
gain a fundamental knowledge of this unusual process and to identify and characterize novel targets for
antiviral therapeutic design. This proposal is driven by the central hypothesis, based on substantial
preliminary data, that both NEC/membrane interactions and NEC oligomerization into a coat are the major
driving forces that enable negative membrane curvature formation and budding. The objective of this proposal
is to systematically dissect the NEC budding mechanism in Herpes Simples virus (HSV) by characterizing
essential protein/protein and protein/membrane interactions and budding intermediates by employing a
multidisciplinary approach, which includes the cutting-edge approaches of cryoelectron microscopy and
electron spin resonance. The scientific premise of the proposed work is that a comprehensive dissection of
the NEC-mediated formation of negative membrane curvature is essential for unraveling the unusual
mechanism of herpesviral nuclear egress and developing strategies to block it. Beyond viruses, this study will
expand our limited mechanistic understanding of the mechanisms of membrane deformation in general. The
proposal is innovative because it investigates an unusual mechanism, is guided by an original hypothesis, and
employs novel approaches. The proposal is significant because it aims to advance our mechanistic
understanding of an essential step in viral replication cycle with the goal of identifying new targets for
therapeutic interventions and because it provides an opportunity to develop models of negative curvature
formation, currently a black box.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ekaterina Heldwein其他文献
Ekaterina Heldwein的其他文献
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{{ truncateString('Ekaterina Heldwein', 18)}}的其他基金
In-vitro analysis of HSV-1 membrane fusion mechanism
HSV-1膜融合机制的体外分析
- 批准号:
10373110 - 财政年份:2021
- 资助金额:
$ 59.58万 - 项目类别:
Structure, antigenicity, and function of HCMV fusogen gB
HCMV融合剂gB的结构、抗原性和功能
- 批准号:
10315349 - 财政年份:2021
- 资助金额:
$ 59.58万 - 项目类别:
In-vitro analysis of HSV-1 membrane fusion mechanism
HSV-1膜融合机制的体外分析
- 批准号:
10230779 - 财政年份:2021
- 资助金额:
$ 59.58万 - 项目类别:
Structure, antigenicity, and function of HCMV fusogen gB
HCMV融合剂gB的结构、抗原性和功能
- 批准号:
10651753 - 财政年份:2021
- 资助金额:
$ 59.58万 - 项目类别:
Structure, antigenicity, and function of HCMV fusogen gB
HCMV融合剂gB的结构、抗原性和功能
- 批准号:
10424572 - 财政年份:2021
- 资助金额:
$ 59.58万 - 项目类别:
Single-particle analysis of HSV-1 membrane fusion mechanism
HSV-1膜融合机制的单粒子分析
- 批准号:
10252827 - 财政年份:2020
- 资助金额:
$ 59.58万 - 项目类别:
Biophysical and structural analysis of the herpesviral nuclear budding machinery
疱疹病毒核出芽机制的生物物理和结构分析
- 批准号:
10159089 - 财政年份:2019
- 资助金额:
$ 59.58万 - 项目类别:
Biophysical and structural analysis of the herpesviral nuclear budding machinery
疱疹病毒核出芽机制的生物物理和结构分析
- 批准号:
10646492 - 财政年份:2019
- 资助金额:
$ 59.58万 - 项目类别:
Structural mechanism of membrane remodeling during herpesvirus nuclear egress
疱疹病毒核排出过程中膜重塑的结构机制
- 批准号:
9037679 - 财政年份:2014
- 资助金额:
$ 59.58万 - 项目类别:
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