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* Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109; and
Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota 55905
To whom requests for reprints should be addressed at Reprint requests should be addressed to either author. William B. Pratt at Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109–0632. David O. Toft at Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905–0001. E-mail: toft{at}mayo.edu
Nearly 100 proteins are known to be regulated by hsp90. Most of these substrates or ‘‘client proteins’’ are involved in signal transduction, and they are brought into complex with hsp90 by a multiprotein hsp90/hsp70-based chaperone machinery. In addition to binding substrate proteins at the chaperone site(s), hsp90 binds cofactors at other sites that are part of the heterocomplex assembly machinery as well as immunophilins that connect assembled substrate•hsp90 complexes to protein-trafficking systems. In the 5 years since we last reviewed this subject, much has been learned about hsp90 structure, nucleotide-binding, and cochaperone interactions; the most important concept is that ATP hydrolysis by an intrinsic ATPase activity results in a conformational change in hsp90 that is required to induce conformational change in a substrate protein. The conformational change induced in steroid receptors is an opening of the steroid-binding cleft so that it can be accessed by steroid. We have now developed a minimal system of five purified proteins—hsp90, hsp70, Hop, hsp40, and p23— that assembles stable receptor•hsp90 heterocomplexes. An hsp90•Hop•hsp70•hsp40 complex opens the cleft in an ATP-dependent process to produce a receptor•hsp90 heterocomplex with hsp90 in its ATP-bound conformation, and p23 then interacts with the hsp90 to stabilize the complex. Stepwise assembly experiments have shown that hsp70 and hsp40 first interact with the receptor in an ATP-dependent reaction to produce a receptor•hsp70•hsp40 complex that is ‘‘primed’’ to be activated to the steroid-binding state in a second ATP-dependent step with hsp90, Hop, and p23. Successful use of the five-protein system with other substrates indicates that it can assemble signal protein•hsp90 heterocomplexes whether the substrate is a receptor, a protein kinase, or a transcription factor. This purified system should facilitate understanding of how eukaryotic hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
Key Words: hsp90 • chaperone proteins • signal transduction • steroid receptors • protein trafficking • protein kinases
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|
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|
|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
 |
|
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|
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|
|
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|
|
|
|
 |
|
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|
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|
|
|
|
|
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|
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|
|
|
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|
|
|
|
 |
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
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|
|
|
|
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|
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