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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 鄧述諄(Shu-Chun Teng) | |
dc.contributor.author | Chen-Yan Hou | en |
dc.contributor.author | 侯辰彥 | zh_TW |
dc.date.accessioned | 2021-06-17T01:17:03Z | - |
dc.date.available | 2020-08-26 | |
dc.date.copyright | 2020-08-26 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-16 | |
dc.identifier.citation | Biebl, M. M. and J. Buchner (2019). 'Structure, Function, and Regulation of the Hsp90 Machinery.' Cold Spring Harb Perspect Biol 11(9). Cereghetti, G. M., et al. (2010). 'Inhibition of Drp1-dependent mitochondrial fragmentation and apoptosis by a polypeptide antagonist of calcineurin.' Cell Death Differ 17(11): 1785-1794. Chen, Y. C., et al. (2018). 'Glucose intake hampers PKA-regulated HSP90 chaperone activity.' Elife 7. Harris, S. F., et al. (2004). 'The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site.' Structure 12(6): 1087-1097. He, J., et al. (2018). 'Assembly of the membrane domain of ATP synthase in human mitochondria.' Proc Natl Acad Sci U S A 115(12): 2988-2993. Meunier, L., et al. (2002). 'A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins.' Mol Biol Cell 13(12): 4456-4469. Mick, D. U., et al. (2010). 'Coa3 and Cox14 are essential for negative feedback regulation of COX1 translation in mitochondria.' J Cell Biol 191(1): 141-154. Panaretou, B., et al. (2002). 'Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1.' Mol Cell 10(6): 1307-1318. Prodromou, C. (2016). 'Mechanisms of Hsp90 regulation.' Biochem J 473(16): 2439-2452. Prodromou, C., et al. (1997). 'Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone.' Cell 90(1): 65-75. Prodromou, C., et al. (1999). 'Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones.' Embo j 18(3): 754-762. Riggs, D. L., et al. (2007). 'Noncatalytic role of the FKBP52 peptidyl-prolyl isomerase domain in the regulation of steroid hormone signaling.' Mol Cell Biol 27(24): 8658-8669. Schopf, F. H., et al. (2017). 'The HSP90 chaperone machinery.' Nat Rev Mol Cell Biol 18(6): 345-360. Shen, Y. and L. M. Hendershot (2005). 'ERdj3, a stress-inducible endoplasmic reticulum DnaJ homologue, serves as a cofactor for BiP's interactions with unfolded substrates.' Mol Biol Cell 16(1): 40-50. Verba, K. A., et al. (2016). 'Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase.' Science 352(6293): 1542-1547. Dickson, Veronica Kane et al. (2006). 'On the structure of the stator of the mitochondrial ATP synthase.' The EMBO journal 25(12): 2911-8. Walker J. E. (2013). 'The ATP synthase: the understood, the uncertain and the unknown. Biochemical Society transactions.' Biochem Soc Trans 41(1): 1–16. Riggs, Daniel L et al. (2003) 'The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. ' The EMBO journal 22(5): 1158-67. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67006 | - |
dc.description.abstract | 熱休克蛋白90 (HSP90) 在真核生物中具有高度的保留性,其功能參與了細胞中許多重要機制,包括蛋白質的折疊與運送、訊息傳導以及蛋白質降解等。且由於許多HSP90之受質被發現與人類疾病如免疫發炎反應、神經退化性疾病、囊腫性纖維化等有關,使得越來越多研究以熱休克蛋白作為潛在治療標的。在熱休克蛋白90執行其摺疊機制時,需要一群輔助摺疊蛋白的協助以調控熱休克蛋白之活性並且改變其構型,其中,某些輔助摺疊蛋白也被發現具有召集與結合特定受質的能力。在先前研究中,IME2依賴性訊息蛋白 (Ids2) 被認為是HSP90之輔助摺疊蛋白,且其磷酸化能影響Hsp90之水解ATP之活性並影響HSP90與Ids2間的結合。研究中也觀察到在剔除IDS2之酵母菌株具有粒線體失能的現象,然而當中之分子機制仍尚未被研究透徹。因此,本研究透過篩選與粒線體與呼吸作用相關之蛋白質尋找Ids2之潛在受質,透過細胞外蛋白質交互作用證實了ATP生成酶γ次單位 (Atp3) 為其主要受質之一,並進一步尋找出兩者進行結合的位置。 | zh_TW |
dc.description.abstract | Heat shock protein 90 (HSP90) is highly conserved in eukaryotes. Its functions involve in protein folding, signal transduction, and protein degradation. Many of its clients play essential roles in disease formation such as inflammation, neurodegenerative diseases and cystic fibrosis. Thus, many studies focus on drugs modulating HSP90. Co-chaperones bind to HSP90 to regulate its ATPase activity and conformational cycle, and some recruit and fold particular clients. Previous evidence suggested that IME2-Dependent Signaling protein 2 (Ids2) is a co-chaperone of HSP90, and Ids2-S148 phosphorylation represses the ATPase activity of Hsc82 by preventing the physical interaction between Ids2 and Hsc82. While mitochondrial defect was observed in ids2Δ cells, the mechanism of how Ids2 regulate mitochondria functions is still enigmatic. In this study, we screened for mitochondria-related and respiratory-related proteins to identify the potential clients of Ids2. Atp3 was identified as one of a major client through in vitro proteins interaction. The interacting domains of Ids2 and Atp3 were also confirmed. These results demonstrate why Ids2 is essential to mitochondria maintenance. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:17:03Z (GMT). No. of bitstreams: 1 U0001-1608202021550700.pdf: 2370916 bytes, checksum: 0510624e3a8cbfb3ef349aec082efe2d (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 口試委員會審定書 i 中文摘要 ii Abstract iii Contents iv Introduction 1 Materials and methods 4 Results 8 Discussion 12 Figures 15 Tables 24 Appendix 26 References 32 | |
dc.language.iso | en | |
dc.title | 輔助摺疊蛋白Ids2負責穩定粒線體複合體IV/V中之受質 | zh_TW |
dc.title | Ids2 co-chaperone stabilizes clients in mitochondrial complex IV/V | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳青錫(Ching-Shyi Wu),林敬哲(Jing-Jer Lin) | |
dc.subject.keyword | 熱休克蛋白,輔助摺疊蛋白,Ids2,ATP生成酶,Atp3, | zh_TW |
dc.subject.keyword | chaperones,co-chaperone,Ids2,ATP synthase,Atp3, | en |
dc.relation.page | 33 | |
dc.identifier.doi | 10.6342/NTU202003619 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-17 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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