Exploiting bacterial effector proteins to study human ubiquitin signaling
Exploiting bacterial effector proteins to study human ubiquitin signaling
批准号:
10625440
负责人:
Jonathan N Pruneda
金额:
$38.5万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-07-01 至 2026-05-31
关键词:
BacteriaBacterial InfectionsBacterial InterferenceBiochemicalBiologyCase StudyCell Cycle RegulationCell physiologyDiseaseEnzymesFeedsHealthHumanHuman BiologyInvadedLifeMotivationOutcomePlayPolymersProcessProteinsRegulationResearchRoleSignal TransductionSignaling MoleculeSpecificitySystemUbiquitinUbiquitinationVisionWorkhuman diseaseinnovationnovelpathogenic bacteriapressureprotein degradationstemtool
中文摘要
项目摘要
通过泛素化的翻译后信号传导对所有真核生物都是必不可少的,
过程可能导致严重的疾病。泛蛋白信号在许多领域的深远重要性
细胞过程源于其形成一组不同的聚合链的能力,
结果。泛素信号的复杂性大大超过了我们对其调控的理解,
细胞结果。虽然一些泛素链类型的信号作用是已知的(例如蛋白质降解
或细胞周期调控),许多所谓的“非典型”链的功能仍然是一个谜,尽管
几十年的研究。作为研究基础人类生物学的另一种方法,我们研究了
入侵病原菌和宿主泛素信号网络之间的相互作用。除了一
一系列其他泛素靶向活性,以支持感染细菌已经进化分泌效应蛋白
组装和去除宿主泛素信号,在某些情况下,
泛素链类型。我们认为,泛素靶向的细菌效应器代表了丰富的机会,
从“由外向内”的角度研究人类泛素信号传导。为了探索这个机会,我们
开发了一种多管齐下的方法,已经确定了新的泛素靶向活动,
细菌病原体使用结构和生物化学的方法,我们将解释的机制,
这些细菌酶的特异性,在这一点上,他们将被用作案例研究和工具,以扩大
我们的工作对破译的监管和信号的复杂性,人类遍在蛋白系统。我们
创新的方法来研究泛素生物学发挥了我们的优势,在其生化机制,
调控,并利用强大的进化压力放在细菌篡夺特定方面的主机
泛素信号在接下来的五年里,我们将展示细菌泛素靶向的广泛性。
活动和他们的实用性,解剖错综复杂的泛素信号,这有助于我们更大的视野,
了解细菌干扰宿主信号传导过程的动机和后果。
英文摘要
Project Summary
Post-translational signaling through ubiquitination is essential to all eukaryotic life, and dysregulation of this
process can lead to severe forms of disease. The far-reaching importance of ubiquitin signaling across many
cellular processes stems from its ability to form a diverse set of polymeric chains that signal for distinct
outcomes. The complexity of ubiquitin signaling vastly outweighs our understanding of its regulation and
cellular outcomes. While the signaling roles for some ubiquitin chain types are known (e.g. protein degradation
or cell cycle regulation), the functions of many so-called `atypical' chains have remained a mystery despite
decades of research. As an alternative approach to studying fundamental human biology, we study the
interactions between invading pathogenic bacteria and the host ubiquitin signaling network. In addition to a
range of other ubiquitin-targeted activities, to support infection bacteria have evolved secreted effector proteins
to assemble and remove host ubiquitin signals, in some cases with exquisite specificity toward discrete
ubiquitin chain types. We propose that ubiquitin-targeted bacterial effectors represent a rich opportunity to
study human ubiquitin signaling from an `outside-in' perspective. To explore this opportunity, we have
developed a multipronged approach that has identified novel ubiquitin-targeted activities among important
bacterial pathogens. Using structural and biochemical approaches we will explain the mechanisms and
specificities of these bacterial enzymes, at which point they will be used as case studies and tools to extend
our work toward deciphering the regulatory and signaling complexities of the human ubiquitin system. Our
innovative approach to studying ubiquitin biology plays to our strengths in the biochemical mechanisms of its
regulation, and leverages the strong evolutionary pressure placed on bacteria to usurp specific aspects of host
ubiquitin signaling. Over the next five years we will demonstrate the breadth of bacterial ubiquitin-targeted
activities and their utility for dissecting the intricacies of ubiquitin signaling, which feeds into our larger vision of
understanding the motivations and ramifications of bacterial interference in host signaling processes.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
Observing Real-Time Ubiquitination in High Throughput with Fluorescence Polarization.
通过荧光偏振观察高通量实时泛素化。
DOI:
10.1007/978-1-0716-2784-6_1
发表时间:
2023
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
作者:
[Franklin,TylerG, Pruneda,JonathanN]
通讯作者:
Pruneda,JonathanN
Interplay between septins and ubiquitin-mediated xenophagy during Shigella entrapment.
志贺氏菌捕获过程中败血症与泛素介导的异体吞噬之间的相互作用。
DOI:
10.1080/27694127.2023.2213541
发表时间:
2023
期刊:
Autophagy reports
影响因子:
--
作者:
[Lobato-Márquez,Damián, Conesa,JoséJavier, López-Jiménez,AnaTeresa, Divine,MichaelE, Pruneda,JonathanN, Mostowy,Serge]
通讯作者:
Mostowy,Serge
DOI:
10.1242/jcs.261139
发表时间:
2023-04-01
期刊:
Journal of cell science
影响因子:
4
作者:
[Lobato-Márquez D, Conesa JJ, López-Jiménez AT, Divine ME, Pruneda JN, Mostowy S]
通讯作者:
Mostowy S
Exploiting bacterial effector proteins to study human ubiquitin signaling
-
批准号:10436347
-
项目类别:
-
资助金额:$38.5万
-
财政年份:2021
-
负责人:Jonathan N Pruneda
-
依托单位:
Exploiting bacterial effector proteins to study human ubiquitin signaling
-
批准号:10272632
-
项目类别:
-
资助金额:$38.5万
-
财政年份:2021
-
负责人:Jonathan N Pruneda
-
依托单位:
Exploiting bacterial effector proteins to study human ubiquitin signaling
-
批准号:10580224
-
项目类别:
-
资助金额:$16.45万
-
财政年份:2021
-
负责人:Jonathan N Pruneda
-
依托单位:
ASSESSING E2~UBIQUITIN DYNAMICS USING SMALL ANGLE X-RAY SCATTERING
-
批准号:8362367
-
项目类别:
-
资助金额:$0.08万
-
财政年份:2011
-
负责人:Jonathan N Pruneda
-
依托单位:
海外基金