Essential roles of Leu/Ile/Phe-rich domain of JC virus agnoprotein in dimer/oligomer formation, protein stability and splicing of viral transcripts

详细信息    查看全文

• 作者：A. Sami Saribas ; Magid Abou-Gharbia ; Wayne Childers ; Ilker K. Sariyer ; Martyn K. White ; Mahmut Safak
• 关键词：Polyomavirus JCV ; SV40 ; BKV ; Merkel cell carcinoma virus ; Large T antigen ; Agnoprotein ; Transcription ; DNA replication ; Progressive multifocal leukoencephalopathy ; Splicing ; Stable dimer formation ; Stable oligomer formation
• 刊名：Virology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：443
• 期：1
• 页码：161-176
• 全文大小：2428 K

文摘

Agnoprotein is one of the key regulatory proteins of polyomaviruses, including JCV, BKV and SV40 and is required for a productive viral life cycle. We have recently reported that agnoprotein forms stable dimer/oligomers mediated by a predicted amphipathic ¦Á-helix, spanning amino acids (aa), 17 to 42. Deletion of the ¦Á-helix renders a replication incompetent virus. Here, we have further characterized this region by a systematic deletion and substitution mutagenesis and demonstrated that a Leu/Ile/Phe-rich domain, (spanning aa 28-39) within ¦Á-helix is indispensable for agnoprotein structure and function. Deletion of aa 30-37 severely affects the dimer/oligomer formation and stable expression of the protein. Mutagenesis data also indicate that the residues, 34-36, may be involved in regulation of the splicing events of JCV transcripts. Collectively, these data suggest that the Leu/Ile/Phe-rich domain plays critical roles in agnoprotein function and thus represents a potential target for developing novel therapeutics against JCV infections.