Assembly of Biological Iron-Sulfur Clusters
生物铁硫簇的组装
基本信息
- 批准号:7641880
- 负责人:
- 金额:$ 28.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-01-01 至 2013-03-31
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAddressAnabolismAnemiaAtaxiaAttentionAzotobacter vinelandiiBindingBiochemicalBiogenesisBiologicalBiological AssayCarbonChloroplastsCircular DichroismComplementCoupledCrystallographyDefectDiseaseDisulfidesElectron Spin Resonance SpectroscopyElectron TransportEnzymesGenerationsGoalsHealthHomeostasisHumanHydrogenIn VitroIronIron OverloadIron-Sulfur ProteinsLifeMagnetismMass Spectrum AnalysisMediatingMediationMetabolismMitochondriaMolecularMolecular BiologyMolecular Biology TechniquesMyopathyNatureNitrogenNitrogen FixationNitrogen Fixation GenesOrganismOxidation-ReductionOxidoreductaseOxygenPlant ProteinsProcessPropertyProsthesisProteinsRegulationRespiratory ChainRoleScaffolding ProteinSignal TransductionSiteSpecificityStagingStructureSulfidesSulfurSystemTechniquesTemperatureThioredoxinWorkX-Ray Crystallographyabsorptionbasecircular magnetic dichroismcysteine desulfurasedesignglutaredoxinhuman diseasein vivonovelpolypeptidepublic health relevancerepairedresearch studyrespiratorystem
项目摘要
DESCRIPTION (provided by applicant):
Project Summary Iron-sulfur clusters are present in more than 200 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Hence the process of iron-sulfur biosynthesis is essential to almost all forms of life and is remarkably conserved in prokaryotic and eukaryotic organisms. Three distinct types of iron-sulfur cluster assembly machinery have emerged, termed the NIF, ISC and SUF systems, and in each case the overall mechanism involves cysteine desulfurase-mediated assembly of transient clusters on scaffold proteins and subsequent transfer of preformed clusters or cluster fragments to apo proteins. However, in no case is the assembly or transfer mechanism understood at the molecular level. The long-term goal of this project is a molecular- level understanding of iron-sulfur cluster biosynthesis using the NIF, ISC and SUF systems. Elucidating the mechanism of iron-sulfur cluster biosynthesis is central to understanding cellular iron homeostasis and thereby human diseases associated with iron-overload and defects in the mitochondrial respiratory chain. The approach involves using molecular biology techniques to effect large scale expression and/or site-specific changes in the target enzymes and proteins, biochemical and enzymatic assays, X-ray crystallography, and the application of biophysical spectroscopic techniques (electron paramagnetic resonance, absorption, magnetic and natural circular dichroism, resonance Raman, and M"ssbauer) that can probe the nature and detailed properties of iron or iron-sulfur centers during cluster biosynthesis or transfer to acceptor proteins. The objectives are to establish the structure of cluster-bound forms and the molecular mechanism of cluster assembly and transfer for each the four known types of iron-sulfur cluster scaffold proteins, identify the roles and specificity of each type of scaffold protein in the maturation of iron-sulfur proteins, and characterize the mechanisms used to regulate iron-sulfur cluster biosynthesis. PUBLIC HEALTH RELEVANCE: The importance of iron-sulfur clusters to human health stems largely from their crucial role in iron homeostasis and their involvement in a large number of enzymes and proteins, particularly those in the mitochondrial respiratory chain. A molecular-level understanding of iron-sulfur cluster biogenesis is crucial for understanding a variety of human diseases involving anemias, myopathies and ataxias that arise from defects in iron-sulfur cluster assembly proteins.
描述(由申请人提供):
铁硫簇存在于200多种不同类型的酶或蛋白质中,是最古老、最普遍、结构最多样的一类生物辅基。因此,铁硫生物合成过程是几乎所有生命形式所必需的,并且在原核生物和真核生物中非常保守。已经出现了三种不同类型的铁-硫簇组装机制,称为NIF、ISC和SUF系统,并且在每种情况下,总体机制都涉及半胱氨酸脱硫酶介导的支架蛋白上的瞬时簇的组装以及随后将预先形成的簇或簇片段转移到载脂蛋白。然而,在任何情况下,都不能在分子水平上理解组装或转移机制。该项目的长期目标是使用NIF、ISC和SUF系统在分子水平上理解铁硫簇生物合成。阐明铁硫簇生物合成的机制对于理解细胞铁稳态以及与线粒体呼吸链中的铁过载和缺陷相关的人类疾病至关重要。该方法涉及使用分子生物学技术来实现目标酶和蛋白质的大规模表达和/或位点特异性变化、生物化学和酶测定、X射线晶体学以及生物物理光谱技术的应用(电子顺磁共振,吸收,磁性和自然圆二色性,共振拉曼,和穆斯堡尔谱),可以探测在簇生物合成或转移到受体蛋白质期间铁或铁-硫中心的性质和详细性质。本研究的目的是建立四种已知的铁硫簇支架蛋白的簇结合形式的结构和簇组装和转移的分子机制,确定每种类型的支架蛋白在铁硫蛋白成熟中的作用和特异性,并表征用于调节铁硫簇生物合成的机制。公共卫生相关性:铁硫簇对人类健康的重要性主要源于它们在铁稳态中的关键作用以及它们参与大量酶和蛋白质,特别是线粒体呼吸链中的酶和蛋白质。铁硫簇生物发生的分子水平的理解是至关重要的,了解各种人类疾病,包括贫血,肌病和共济失调,所产生的铁硫簇组装蛋白的缺陷。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MICHAEL K. JOHNSON其他文献
MICHAEL K. JOHNSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MICHAEL K. JOHNSON', 18)}}的其他基金
Recruitment of a Bioinorganic Chemistry Faculty Member
招聘生物无机化学教员
- 批准号:
7945286 - 财政年份:2009
- 资助金额:
$ 28.91万 - 项目类别:
Recruitment of a Bioinorganic Chemistry Faculty Member
招聘生物无机化学教员
- 批准号:
7859304 - 财政年份:2009
- 资助金额:
$ 28.91万 - 项目类别:
ASSEMBLY AND FUNCTION OF BIOLOGICAL IRON-SULFUR CLUSTERS
生物铁硫簇的组装和功能
- 批准号:
6254773 - 财政年份:2001
- 资助金额:
$ 28.91万 - 项目类别:
ASSEMBLY AND FUNCTION OF BIOLOGICAL IRON-SULFUR CLUSTERS
生物铁硫簇的组装和功能
- 批准号:
6490169 - 财政年份:2001
- 资助金额:
$ 28.91万 - 项目类别:
ASSEMBLY AND FUNCTION OF BIOLOGICAL IRON-SULFUR CLUSTERS
生物铁硫簇的组装和功能
- 批准号:
6692650 - 财政年份:2001
- 资助金额:
$ 28.91万 - 项目类别:
Assembly and Repair of Biological Iron-Sulfur Clusters
生物铁硫簇的组装和修复
- 批准号:
8760507 - 财政年份:2001
- 资助金额:
$ 28.91万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 28.91万 - 项目类别:
Research Grant