Regulation of Epstein-Barr Virus Capsid Protein BDLF1 by Small Ubiquitin-like Modifier Proteins

• Main Authors: Han-Ting Chen, 陳菡亭
• Other Authors: 張麗冠
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/mbxt7a

碩士 === 國立臺灣大學 === 生化科技學系 === 100 === Epstein-Barr virus (EBV), also called human herpesvirus 4 (HHV-4), contains a common icosahedral structure with 162 capsomers. The capsids of EBV contain major capsid protein VCA and minor capsid proteins, BDLF1 and BORF1. The capsomers are composed of VCA pentamers or hexamers, which are linked together by triplexes that are formed by two copies of BDLF1 and one copy of BORF1. During the capsid assembly, BORF1, which exhibits nuclear localization signal sequence (NLS) brings VCA and BDLF1 into the nuclei. Assembly of capsid is required for the development of mature EBV virion but it is nevertheless the must unknown part of EBV lytic cycle. Targets covently attached by small ubiquitin-like modifier (SUMO) proteins is a kind of post-translational modification which involves in diverse functions of proteins including cellular localization, stability, transcriptional activity and protein-protein interaction. This study demonstrates that minor capsid proteins BDLF1 and BORF1 are both SUMOylated. A GST pulldown study identifies BDLF1 interacts noncolvently with SUMO through SUMO-interaction motifs (SIM) in the N-terminal region of BDLF1. Functional analysis of BDLF1 SIM mutants revealed that SIM integrity is required for increasing the SUMOylation level, decreasing the ubiquitination level as well as maintaining the stability of BDLF1. Futhermore, immunofluorescence analysis shows that BDLF1 SIM mutants exhibit different pattern with the colocalization of wt-BDLF1 and BORF1. These results indicate the SIM motifs in BDLF1 are likely to have a key function in the EBV capsid assembly.