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J. Biol. Chem., Vol. 275, Issue 41, 31682-31688, October 13, 2000
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From the 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.
Heat Shock Protein 90 Mediates Protein-protein Interactions
between Human Aminoacyl-tRNA Synthetases*
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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
*
This work was supported in part by a grant from the National
Creative Research Initiatives of the Ministry of Science and Technology
of Korea (to S. K.) and by a grant from the Korea Science and
Engineering Foundation (H. J. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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