Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases.
Heat shock protein 90 (hsp90) is a molecular chaperone responsible for protein folding and maturation in vivo. Interaction of hsp90 with human glutamyl-prolyl-tRNA synthetase (EPRS) was found by genetic screening, co-immunoprecipitation, and in vitro binding experiments. This interaction was sensitive to the hsp90 inhibitor, geldanamycin, and also ATP, suggesting that the chaperone activity of hsp90 is required for interaction with EPRS. Interaction of EPRS with hsp90 was targeted to the region of three tandem repeats linking the two catalytic domains of EPRS that is also responsible for the interaction with isoleucyl-tRNA synthetase (IRS). Interaction of EPRS and IRS also depended on the activity of hsp90, implying that their association was mediated by hsp90. EPRS and IRS form a macromolecular protein complex with at least six other tRNA synthetases and three cofactors. hsp90 preferentially binds to most of the complex-forming enzymes rather than those that are not found in the complex. In addition, inactivation of hsp90 interfered with the in vivo incorporation of the nascent aminoacyl-tRNA synthetases into the multi-ARS complex. Thus, hsp90 appears to mediate protein-protein interactions of mammalian tRNA synthetases.
Kang
J
J
National Creative Research Initiatives Center for ARS Network, Sung Kyun Kwan University, Suwon 440-746 and the Department of Bioscience and Biotechnology, Sejong University, 98 Kunjadong, Kwangjingu, Seoul 143-747, Korea.
Kim
T
T
Ko
Y G
YG
Rho
S B
SB
Park
S G
SG
Kim
M J
MJ
Kwon
H J
HJ
Kim
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D016227:Benzoquinones; D001665:Binding Sites; D002417:Cattle; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D046911:Macromolecular Substances; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011809:Quinones / Q000494:pharmacology; D013379:Substrate Specificity; D020080:Tandem Repeat Sequences; D020798:Two-Hybrid System Techniques; D015003:Yeasts
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D006877:Hydroxamic Acids; D047029:Lactams, Macrocyclic; D007783:Lactones; D018942:Macrolides; D046911:Macromolecular Substances; D011809:Quinones; C012589:trichostatin A; D000255:Adenosine Triphosphate; D000604:Amino Acyl-tRNA Synthetases; C415462:glutamyl-prolyl-tRNA synthetase; C035359:monorden; C001277:geldanamycin