Phosphorylation State-Dependent interactions of hepadnavirus core protein with host factors

Laurie Ludgate, Christina Adams, Jianming Hu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Dynamic phosphorylation and dephosphorylation of the hepadnavirus core protein C-terminal domain (CTD) are required for multiple steps of the viral life cycle. It remains unknown how the CTD phosphorylation state may modulate core protein functions but phosphorylation state-dependent viral or host interactions may play a role. In an attempt to identify host factors that may interact differentially with the core protein depending on its CTD phosphorylation state, pulldown assays were performed using the CTD of the duck hepatitis B virus (DHBV) and human hepatitis B virus (HBV) core protein, either with wild type (WT) sequences or with alanine or aspartic acid substitutions at the phosphorylation sites. Two host proteins, B23 and I2PP2A, were found to interact preferentially with the alanine-substituted CTD. Furthermore, the WT CTD became competent to interact with the host proteins upon dephosphorylation. Intriguingly, the binding site on the DHBV CTD for both B23 and I2PP2A was mapped to a region upstream of the phosphorylation sites even though B23 or I2PP2A binding to this site was clearly modulated by the phosphorylation state of the downstream and non-overlapping sequences. Together, these results demonstrate a novel mode of phosphorylation-regulated protein-protein interaction and provide new insights into virus-host interactions.

Original languageEnglish (US)
Article numbere29566
JournalPloS one
Volume6
Issue number12
DOIs
StatePublished - Dec 22 2011

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

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