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標題: | 輔助摺疊蛋白Ids2負責穩定粒線體複合體IV/V中之受質 Ids2 co-chaperone stabilizes clients in mitochondrial complex IV/V |
作者: | Chen-Yan Hou 侯辰彥 |
指導教授: | 鄧述諄(Shu-Chun Teng) |
關鍵字: | 熱休克蛋白,輔助摺疊蛋白,Ids2,ATP生成酶,Atp3, chaperones,co-chaperone,Ids2,ATP synthase,Atp3, |
出版年 : | 2020 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67006 |
DOI: | 10.6342/NTU202003619 |
全文授權: | 有償授權 |
顯示於系所單位: | 微生物學科所 |
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