Wb. Pratt et Kd. Dittmar, STUDIES WITH PURIFIED CHAPERONES ADVANCE THE UNDERSTANDING OF THE MECHANISM OF GLUCOCORTICOID RECEPTOR HSP90 HETEROCOMPLEX ASSEMBLY, Trends in endocrinology and metabolism, 9(6), 1998, pp. 244-252
The study of the 9S, untransformed state of steroid receptors has led
to the discovery of a multiprotein chaperone system that assembles het
erocomplexes between hsp90 and a variety of proteins involved in signa
l transduction. Using the formation of glucocorticoid receptor (GR)-hs
p90 heterocomplexes as a model, we have reconstituted a fully function
al heterocomplex assembly system from purified components. The basic a
ssembly system requires four proteins - hsp90, hsp70, p60/Hop and hsp4
0 - to assemble GR-hsp90 heterocomplexes, which are then stabilized by
the hsp90-interacting protein p23. The four proteins can self-assembl
e into an hsp90-p60/Hop-hsp70-hsp40 complex that we call a foldosome.
Foldosomes isolated from reticulocyte lysate or formed from purified p
roteins open up a steroid-binding pocket to create a high-affinity ste
roid-binding state of the GR. We describe here the systematic reconsti
tution of the hsp90-based chaperone machinery and develop a model of t
he receptor-hsp90 heterocomplex assembly mechanism.