Essential Roles of Leu/Ile/Phe-rich Domain of JC Virus Agnoprotein in Dimer/oligomer Formation, Protein Stability and Splicing of Viral Transcripts

Overview

Journal Virology

Specialty Microbiology

Date 2013 Jun 11

PMID 23747198

Citations 20

Authors

A Sami Saribas

Magid Abou-Gharbia

Wayne Childers

Ilker K Sariyer

Martyn K White

Mahmut Safak

Affiliations

Soon will be listed here.

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.

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