Allosteric and Transport Mechanisms in TonB-dependent Transporters

TonB 依赖性转运蛋白的变构和转运机制

基本信息

  • 批准号:
    9019305
  • 负责人:
  • 金额:
    $ 38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-12-01 至 2020-11-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Active membrane transport of essential compounds such as molecules and proteins into the cell is a fundamental process in cellular physiology and is thus regulated by a number of different transport pathways. Gram-negative bacteria, mitochondria, and chloroplasts contain transmembrane β-barrel proteins on their outer membrane (OM), commonly referred to as outer membrane proteins (OMPs), that serve essential functions in cargo transport and signaling. A large and important family of OMPs are the TonB-dependent transporters (TBDTs). TBDTs are involved primarily in iron uptake, a metal that is essential for the growth and development of almost all living organisms. In addition, TBDTs also transport naturally occurring antibiotics, colicins and phages. Because iron transport systems are critical for the survival of a large number of pathogenic bacteria in vivo, TBDTs are attractive candidates for therapeutic intervention. Moreover, antibiotics are currently being produced that target TBDTs and rely on them for their transport inside the cell. Therefore, this system has attracted tremendous interest for medical and biotechnological reasons. Numerous studies have focused on dissecting the mechanisms underpinning transport of substrates through the pore of TBDTs. TBDTs share a common structure consisting of a transmembrane β-barrel and a globular domain, the so-called plug, that occludes the lumen of the barrel. The periplasmic N terminus of TBDTs contains a sequence, the so-called TonB box, which recruits the periplasmic domain of TonB. This binding event is absolutely essential for the transport. Over 50 crystal structures of TBDTs in various liganded states are available but in all of them the pore is always occluded. How TonB binding to TBDTs enables substrate translocation remains a mystery. We propose to use NMR spectroscopy to dissect the allosteric interactions and unravel the transport mechanisms in FhuA, a prototypic TBDT. We will obtain integrated structural, dynamic, kinetic and thermodynamic information of the interaction between physiological substrates and the FhuA transporter and study how TonB enables substrate translocation. We present very strong supporting data that the key processes can be characterized by NMR at the atomic level by the use of advanced NMR and isotope labeling methodologies. We aim to: (i) determine the structural dynamics of FhuA by NMR; (ii) characterize the effect of TonB binding on the structure and dynamics of FhuA; (iii) characterize the transport mechanisms of siderophores and antibacterial peptides; (iv) characterize the transport mechanisms of colicins. Successful completion of the specific aims outlined in this proposal will provide unprecedented and fascinating insight into the fundamental mechanisms that enable substrate transport by the large family of TBDTs. A comprehensive description of the structural and mechanistic basis of operation of these proteins will further advance our understanding of how allosteric membrane transporters function and how they are regulated.


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 }}

CHARALAMPOS KALODIMOS其他文献

CHARALAMPOS KALODIMOS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('CHARALAMPOS KALODIMOS', 18)}}的其他基金

Structure and functional mechanisms of molecular chaperones and protein kinases
分子伴侣和蛋白激酶的结构和功能机制
  • 批准号:
    9920188
  • 财政年份:
    2017
  • 资助金额:
    $ 38万
  • 项目类别:
Structure and functional mechanisms of molecular chaperones and protein kinases
分子伴侣和蛋白激酶的结构和功能机制
  • 批准号:
    9515515
  • 财政年份:
    2017
  • 资助金额:
    $ 38万
  • 项目类别:
Structure and functional mechanisms of molecular chaperones and protein kinases
分子伴侣和蛋白激酶的结构和功能机制
  • 批准号:
    10552406
  • 财政年份:
    2017
  • 资助金额:
    $ 38万
  • 项目类别:
Allosteric and Transport Mechanisms in TonB-dependent Transporters
TonB 依赖性转运蛋白的变构和转运机制
  • 批准号:
    9188052
  • 财政年份:
    2015
  • 资助金额:
    $ 38万
  • 项目类别:
Structural insight into novel mechanisms of type III secretion
III 型分泌新机制的结构洞察
  • 批准号:
    8580192
  • 财政年份:
    2011
  • 资助金额:
    $ 38万
  • 项目类别:
Structural insight into novel mechanisms of type III secretion
III 型分泌新机制的结构洞察
  • 批准号:
    8775192
  • 财政年份:
    2011
  • 资助金额:
    $ 38万
  • 项目类别:
Structural insight into novel mechanisms of type III secretion
III 型分泌新机制的结构洞察
  • 批准号:
    10396532
  • 财政年份:
    2011
  • 资助金额:
    $ 38万
  • 项目类别:
Structural insight into novel mechanisms of type III secretion
III 型分泌新机制的结构洞察
  • 批准号:
    8298308
  • 财政年份:
    2011
  • 资助金额:
    $ 38万
  • 项目类别:
Structural insight into novel mechanisms of type III secretion
III 型分泌新机制的结构洞察
  • 批准号:
    8390463
  • 财政年份:
    2011
  • 资助金额:
    $ 38万
  • 项目类别:
Structural insight into novel mechanisms of type III secretion
III 型分泌新机制的结构洞察
  • 批准号:
    8253171
  • 财政年份:
    2011
  • 资助金额:
    $ 38万
  • 项目类别:

相似海外基金

New technologies for targeted delivery of anti-bacterial agents
抗菌药物靶向递送新技术
  • 批准号:
    1654774
  • 财政年份:
    2015
  • 资助金额:
    $ 38万
  • 项目类别:
    Studentship
Targeting bacterial phosphatases for novel anti-bacterial agents.
针对细菌磷酸酶的新型抗菌剂。
  • 批准号:
    8416313
  • 财政年份:
    2012
  • 资助金额:
    $ 38万
  • 项目类别:
Targeting bacterial phosphatases for novel anti-bacterial agents.
针对细菌磷酸酶的新型抗菌剂。
  • 批准号:
    8298885
  • 财政年份:
    2012
  • 资助金额:
    $ 38万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了