Molecular interactions of chaperones as a target for anti-malarial drug development
伴侣分子的分子相互作用作为抗疟疾药物开发的靶标
基本信息
- 批准号:271495877
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2015
- 资助国家:德国
- 起止时间:2014-12-31 至 2019-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Heat shock protein 70 (Hsp70) and Hsp90 are some of the most studied molecular chaperones, proteins which themselves are responsible for the folding of other proteins in the cell. Hsp70 binds non-native proteins whilst substrates of Hsp90 are usually in native-like forms. Proteins that require both Hsp70 and Hsp90 to fold are thus transferred from Hsp70 to Hsp90 during the folding process. Eukaryotic Hsp90 participates in the conformational regulation of signal transduction molecules, such as tyrosine kinases and steroid hormone receptors. For example, steroid hormone receptors associate with Hsp90 in order for them to adopt conformational competence for hormone binding. In addition to Hsp70 and Hsp90, there are numerous co-chaperones and other protein interactors which are essential for the efficient functioning of the chaperone system and thus efficient protein homeostasis. We have previously characterised a P. falciparum homologue of the Hsp70-Hsp90 Organising Protein (PfHop) and analysed its interaction with parasite encoded chaperones. In the previous funding period we were interested in understanding the interaction between PfHop and PfHsp70-1/PfHsp90 with a view to blocking this interaction. Additionally, we wished to establish protein:protein interaction assays for use in drug-screening. In this renewal proposal we propose to continue our analysis of chaperone/co-chaperone interactions in the P. falciparum system, now including one further molecular interactor, PfHsp70-z. Additionally, we shall now use our previously established interaction assays to screen libraries for compounds which block this likely essential molecular interaction.
热休克蛋白70 (Hsp70)和Hsp90是研究最多的分子伴侣蛋白,它们本身负责细胞内其他蛋白质的折叠。Hsp70与非天然蛋白结合,而Hsp90的底物通常以类似天然蛋白的形式存在。因此,需要Hsp70和Hsp90折叠的蛋白质在折叠过程中从Hsp70转移到Hsp90。真核Hsp90参与信号转导分子的构象调节,如酪氨酸激酶和类固醇激素受体。例如,类固醇激素受体与Hsp90结合,使其具有结合激素的构象能力。除了Hsp70和Hsp90之外,还有许多共同伴侣和其他蛋白质相互作用物,它们对于伴侣系统的有效运作和有效的蛋白质稳态至关重要。我们之前已经鉴定了恶性疟原虫Hsp70-Hsp90组织蛋白(PfHop)的同源物,并分析了它与寄生虫编码伴侣蛋白的相互作用。在之前的资助期内,我们有兴趣了解PfHop和PfHsp70-1/PfHsp90之间的相互作用,以期阻断这种相互作用。此外,我们希望建立用于药物筛选的蛋白质:蛋白质相互作用测定法。在这个更新提案中,我们建议继续我们对恶性疟原虫系统中伴侣/共同伴侣相互作用的分析,现在包括一个新的分子相互作用,PfHsp70-z。此外,我们现在将使用我们之前建立的相互作用分析来筛选阻止这种可能的基本分子相互作用的化合物库。
项目成果
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Professor Dr. Jude Marek Przyborski其他文献
Professor Dr. Jude Marek Przyborski的其他文献
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{{ truncateString('Professor Dr. Jude Marek Przyborski', 18)}}的其他基金
Trafficking and sorting of proteins to the parasitophorous vacuolar membrane of the malaria parasite P. falciparum: Exp1 as a model.
疟原虫恶性疟原虫寄生液泡膜上蛋白质的运输和分选:Exp1 作为模型。
- 批准号:
416780686 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Research Grants
The role of host cell proteins in survival and propagation of the human malaria parasite P. falciparum.
宿主细胞蛋白在人类疟原虫恶性疟原虫存活和繁殖中的作用。
- 批准号:
391524768 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grants
Exported chaperones/co-chaperones of P. falciparum: Interaction with host proteins, and relevance for intra-erythrocytic survival of the parasite
恶性疟原虫的输出伴侣/共伴侣:与宿主蛋白的相互作用以及寄生虫红细胞内存活的相关性
- 批准号:
198145107 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Priority Programmes
Investigation of a translocon complex implicated in protein transport to the apicoplast of Plasmodium falciparum
参与蛋白质转运至恶性疟原虫顶质体的易位子复合物的研究
- 批准号:
85997262 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Research Grants
Protein trafficking mechanisms in the human malarial parasite P. falciparum
人类疟疾寄生虫恶性疟原虫的蛋白质运输机制
- 批准号:
29282676 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Priority Programmes
Using new genetic tools to elucidate the importance of exported proteins in intra-erythrocytic survival of the malaria parasite P. falciparum.
使用新的遗传工具阐明输出蛋白对疟疾寄生虫恶性疟原虫红细胞内存活的重要性。
- 批准号:
351262938 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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多维数据辨析法用于兽药与生物大分子作用体系的研究
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- 批准年份:2010
- 资助金额:25.0 万元
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- 批准年份:2009
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
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