title: Essential roles of Leu/Ile/Phe-rich domain of JC virus agnoprotein in dimer/oligomer formation, protein stability and splicing of viral transcripts.
abstract: 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 α-helix, spanning amino acids (aa), 17 to 42. Deletion of the α-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 α-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.
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States.
authors.forename: A
authors.initials: A
authors.lastname: Sami Saribas
authors.forename: Magid
authors.initials: M
authors.lastname: Abou-Gharbia
authors.forename: Wayne
authors.initials: W
authors.lastname: Childers
authors.forename: Ilker K
authors.initials: IK
authors.lastname: Sariyer
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
authors.forename: Mahmut
authors.initials: M
authors.lastname: Safak
mesh_terms: D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D006801:Humans; D007577:JC Virus / Q000502:physiology*; D055503:Protein Multimerization; D055550:Protein Stability; D012326:RNA Splicing; D017384:Sequence Deletion; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins