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Originally published In Press as doi:10.1074/jbc.M909965199 on July 25, 2000

J. Biol. Chem., Vol. 275, Issue 41, 31682-31688, October 13, 2000
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Heat Shock Protein 90 Mediates Protein-protein Interactions between Human Aminoacyl-tRNA Synthetases*

Jeongwoo KangDagger , Taeho KimDagger , Young-Gyu KoDagger , Seung Bae RhoDagger , Sang Gyu ParkDagger , Min Jung Kim§, Ho Jeong Kwon§, and Sunghoon KimDagger

From the Dagger  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

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.


* 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.

To whom correspondence should be addressed: Center for ARS Network, Sung Kyun Kwan University, 300 Chunchundong, Jangangu, Suwon, Kyunggido 440-746, Korea. Tel.: 82-31-290-5681; Fax: 82-31-290-5682; E-mail: shkim@yurim.skku.ac.kr.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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