Intrinsic disorder mediates hepatitis C virus core-host cell protein interactions

摘要: Viral proteins bind to numerous cellular and viral throughout the infection cycle. However, mechanisms by which interact with such large numbers of factors remain unknown. Cellular that multiple, distinct partners often do so through short sequences known as molecular recognition features (MoRFs) embedded within intrinsically disordered regions (IDRs). In this study, we report first evidence MoRFs in play a similar role targeting host cell. Using combination evolutionary modeling, protein–protein interaction analyses forward genetic screening, systematically investigated two computationally predicted N-terminal IDR hepatitis C virus (HCV) Core protein. Sequence analysis showed their conservation across all HCV genotypes canine equine Hepaciviruses. Phylogenetic modeling indicated are under stronger purifying selection than surrounding sequence, suggesting these modules have biological function. yeast two-hybrid assay, identified three binding for each MoRF, including previously characterized targets (DDX3X NPM1). Random site-directed mutagenesis demonstrated MoRF were required proteins, but different residues critical partners. This study viruses may use intrinsic disorder target multiple same amino acid sequence provides framework characterizing other proteomes.