PloS one, 2012-08, Vol.7 (8), p.e42106-e42106
2012
Details
- Autor(en) / Beteiligte
- Titel
- Binding of the heterogeneous ribonucleoprotein K (hnRNP K) to the Epstein-Barr virus nuclear antigen 2 (EBNA2) enhances viral LMP2A expression
- Ist Teil von
- PloS one, 2012-08, Vol.7 (8), p.e42106-e42106
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA- antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV- infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0042106Titel-ID: cdi_plos_journals_1326222676
- Format
- –
- Schlagworte
- Antibodies, Monoclonal - immunology, Antibody Specificity - immunology, Antigenic determinants, Antigens, Arginine, Arginine - analogs & derivatives, Arginine - metabolism, Binding, Biochemistry, Biology, Cell Line, Cell survival, Cellular proteins, Cellular structure, Coding, Conserved sequence, Deoxyribonucleic acid, DNA, DNA - metabolism, DNA methylation, E coli, Environmental health, Enzymes, Epitopes, Epstein-Barr virus, Epstein-Barr Virus Infections - metabolism, Epstein-Barr Virus Nuclear Antigens - chemistry, Epstein-Barr Virus Nuclear Antigens - immunology, Epstein-Barr Virus Nuclear Antigens - metabolism, Gene expression, Gene Expression Regulation, Viral, Glycine, Herpesvirus 4, Human - genetics, Herpesvirus 4, Human - physiology, Heterogeneous-Nuclear Ribonucleoprotein K - metabolism, Homology, Humans, Immunoglobulins, Immunology, Immunoprecipitation, Intensive care, LMP2A protein, Lymphocytes, Lymphocytes B, Medical schools, Medicine, Membrane proteins, Methylation, Molecular Sequence Data, Monoclonal antibodies, Motor neurons, Multiprotein Complexes - metabolism, Mutant Proteins - metabolism, Promoter Regions, Genetic - genetics, Protein Binding, Protein Transport, Proteins, Repetitive Sequences, Amino Acid, Ribonucleoprotein K, snRNP Core Proteins - metabolism, Surface structure, Transcription factors, Transfection, Transformation, Viral Matrix Proteins - genetics, Viral Matrix Proteins - metabolism, Viral Proteins - chemistry, Viral Proteins - immunology, Viral Proteins - metabolism, Virology, Viruses