Co-chaperone BAG3 and adenovirus penton base protein partnership.
The BAG family of Hsp70/Hsc70 co-chaperones is characterised by the presence of a conserved BAG domain at the carboxyl-terminus. BAG3 protein is the only member of this family containing also the N-terminally located WW domain. We describe here the identification of adenovirus (Ad) penton base protein as the first BAG3 partner recognising BAG3 WW domain. Ad penton base is the viral capsid constituent responsible for virus internalisation. It contains in the N-terminal part two conserved PPxY motifs, known ligands of WW domains. In cells producing Ad penton base protein, cytoplasmic endogenous BAG3 interacts with it and co-migrates to the nucleus. Preincubation of BAG3 with Ad base protein results in only slight modulation of BAG3 co-chaperone activity, suggesting that this interaction is not related to the classical BAG3 co-chaperone function. However, depletion of BAG3 impairs the cell entry of the virus and viral progeny production in Ad-infected cells, suggesting that the interaction between virus penton base protein and cellular co-chaperone BAG3 positively influences virus life cycle. These results thus demonstrate a novel host-pathogen interaction, which contributes to the successful infectious life cycle of adenoviruses. In addition, these data enrich our knowledge about the multifunctionality of the BAG3 co-chaperone.
Gout
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Institut de Biologie Structurale, 41 rue Jules Horowitz, CEA, CNRS, Université Joseph Fourier, 38027 Grenoble, France.
Gutkowska
M
M
Takayama
S
S
Reed
J C
JC
Chroboczek
J
J
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000257:Adenoviridae Infections; D051017:Apoptosis Regulatory Proteins; D036022:Capsid Proteins / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D018832:Molecular Chaperones; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D053586:Virus Internalization
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D036022:Capsid Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; C043322:penton protein, adenovirus