title: Hsp90 binds CpG oligonucleotides directly: implications for hsp90 as a missing link in CpG signaling and recognition.
abstract: CpG motifs originating from bacterial DNA (CpG DNA) can act as danger signals for the mammalian immune system. These CpG DNA motifs like many other pathogen-associated molecular patterns are believed to be recognized by a member of the toll-like receptor family, TLR-9. Here we show results suggesting that heat shock protein 90 (hsp90) is also implicated in the recognition of CpG DNA. Hsp90 was characterized as a binder to oligodeoxynucleotides (ODNs) containing CpG motifs (CpG ODNs) after several purification steps from crude protein extracts of peripheral blood mononuclear cells. This finding was further supported by direct binding of CpG ODNs to commercially available human hsp90. Additionally, immunohistochemistry studies showed redistribution of hsp90 upon CpG ODN uptake. Thus, we propose that hsp90 can act as a ligand transfer molecule and/or play a central role in the signaling cascade induced by CpG DNA.
authors.affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institutet, 17177, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Bandholtz
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: C
authors.initials: C
authors.lastname: Palmberg
authors.forename: K
authors.initials: K
authors.lastname: Mattsson
authors.forename: B
authors.initials: B
authors.lastname: Ohlsson
authors.forename: A
authors.initials: A
authors.lastname: High
authors.forename: J
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: D F
authors.initials: DF
authors.lastname: Hunt
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
authors.forename: H
authors.initials: H
authors.lastname: Wigzell
authors.forename: B
authors.initials: B
authors.lastname: Agerberth
authors.forename: G H
authors.initials: GH
authors.lastname: Gudmundsson
mesh_terms: D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004268:DNA-Binding Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D024202:Electrophoretic Mobility Shift Assay; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D036103:Nanotechnology; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051217:Toll-Like Receptor 9; D020298:U937 Cells
chemical_list: C408982:CPG-oligonucleotide; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9