泛素化與類泛素化對Epstein-Barr病毒外鞘蛋白質BDLF1的調控

Regulation of the Epstein-Barr virus capsid protein BDLF1 by ubiquitination and sumoylation

荊士瑋(Shih-Wei Jing)

指導教授 ： 張麗冠

國立臺灣大學/生命科學院/生化科技學系/碩士(2017年)

https://doi.org/10.6342/NTU201800827

摘要

人類第四型皰疹病毒(Epstein-Barr virus, EBV)是第一個被發現的人類致癌病毒，並且能夠長期潛伏於人體的B淋巴球細胞中。EB病毒外殼為一個正二十面體，由VCA組成的12個五聚體與150個六聚體，以及320個由2個BDLF1與1個BORF1所組成的三聚體組裝而成。目前已知BDLF1會被BORF1帶入細胞核中，並於PML nuclear body附近進行組裝。另外先前的研究指出SUMO-1會修飾BDLF1，本研究進一步證明SUMO-2與Ub同樣也會對BDLF1進行修飾。其中，BDLF1的胺基酸K124位置為Ub以及SUMO-2的主要修飾位置，而且BDLF1會藉由SUMO-interacting motifs (SIMs)促進SUMO-2對K124的修飾並與Ub競爭，以提升BDLF1的穩定性。除此之外，BDLF1的SIMs也具有增強與BORF1間結合力的能力。綜合以上結果推論，EB病毒外鞘蛋白質BDLF1上的SIMs對於K124的類泛素化是必要的，並且減少K124的泛素化，以增加BDLF1的半衰期。除此之外，BDLF1的SIMs能夠加強與BORF1的結合。因此，BDLF1可能會透過這兩種策略來提升病毒顆粒的組裝量，進而促進病毒的增殖。

關鍵字

人類皰疹病毒第四型 ； BDLF1 ； 泛素化 ； 類泛素化

並列摘要

Epstein-Barr virus　(EBV) is the first discovered oncogenic virus and infect human B cells. EBV contains an icosahedral nucleocapsid which is composed by 12 pentameric, 150 hexameric capsomers and 320 triplexes. These capsomers are composed by the major capsid protein, VCA, and connected by triplexes forming by two minor capsid proteins, BORF1 and BDLF1. A previous study indicated that BDLF1interacts with BORF1, and then the proteins were transported to the PML nuclear bodies in the nucleus for the capsid assembly. BDLF1 has also been shown to be modified by SUMO-1. This study further demonstrated that BDLF1 is modified by SUMO-2 and ubiquitin. The BDLF1 K124 is the main modification site of SUMO-2 and ubiquitin. Moreover, the SUMO-interacting motifs (SIMs) of BDLF1 are required for the sumoylation of BDLF1, but not the ubiquitination of BDLF1, which thereby increases the stability of BDLF1. Additionally, BDLF1 SIMs promote the interaction of BDLF1 with BORF1, which may facilitate capsid assembly and virus proliferation.

並列關鍵字

Epstein-Barr virus ； BDLF1 ； ubiquitination ； sumoylation

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