HBV X protein interacts with cytoskeletal signaling proteins through SH3 binding.
The aim of this study was to investigate interactions between cellular SH3-containing proteins and the proline-rich domain in Hepatitis B Virus (HBV) X protein (HBx) The proline-rich domain of HBx (amino acids 19-58) as well as the relevant site-directed mutagenesis (proline to alanine residues) were cloned into pGEX-5X-1 and expressed as GST-PXXP and GST-AXXA probes. Panomics SH3 domain arrays were probed using both GST-PXXP and GST-AXXA to identify potential interacting SH3 domain containing proteins. The specific interactions were confirmed by the immunoprecipitation of the full-length SH3 domain-containing protein. We report here the binding assay which demonstrated interaction between PXXP domain in HBx and the SH3-domain containing proteins, in particular various signaling proteins involved in cytoskeletal reorganization. Our findings were consistent with similar virus-host interactions via SH3 binding for other viruses such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV) Further characterization of the proline-rich binding to SH3 domains could yield important information for the design of novel therapeutic measures against downstream disease causative effects of HBx in the liver cells.
Feng
Huixing
H
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459.
Tan
Tuan Lin
TL
Niu
Dandan
D
Chen
Wei Ning
WN
D045744:Cell Line, Tumor; D051356:Cortactin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009841:Oligonucleotides / Q000235:genetics; D055232:Proline-Rich Protein Domains / Q000235:genetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D018909:src Homology Domains / Q000235:genetics / Q000502:physiology*
D051356:Cortactin; D003598:Cytoskeletal Proteins; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D005982:Glutathione Transferase