Figure 1: Steroid Receptor•Hsp90 Assembly. The glucocorticoid receptor (GR) is shown as a standard model. The chaperones Hsp90 and Hsp70 (and their associated cochaperone Hsp40) are assembled thanks to the presence of Hop/p60 (heat-shock organizing protein, formerly called p60). Hop/p60 has tetratricopeptide repeats (TPR) and is absolutely required to bring the two master chaperones together. This assembly can be reached spontaneously by mixing all proteins in buffer. When this basic complex is not associated to the GR, the receptor cannot bind hormone (H, yellow sphere) because its ligand-binding domain is collapsed, but the transference of the chaperone complex to the receptor in an ATP- and K+-dependent manner opens the receptors cleft that can be accessed by hormone. The small acidic protein p23 stabilizes the complex when it is bound to Hsp90 dimers. Even though the chaperone complex can be transferred as a block to the GR, it can also be primed by Hsp70•Hsp40, and then the Hsp90•p23 complex is recruited. When the GR is properly folded and able to bind steroid, Hop/p60 is released from the complex leaving the TPR acceptor site on the Hsp90 dimer available, which is occupied by a TPR-domain immunophilin (IMM) to form the `mature' final complex. BAG-1 (Bcl-2- associated gene product-1), an Hsp70-binding protein, promotes the release of Hop/p60 from the complex without inhibiting GR•Hsp90 heterocomplex assembly. The release of Hop/p60 can be prevented by Hip (Hsp70-interacting protein), a BAG-1 antagonistic cochaperone. Neither BAG-1 nor Hip are essential for the final folding of the heterocomplex and are not present in the mature form of the GR•Hsp90 complex, but they play regulatory roles on the dynamic assembly of the heterocomplex and the termination of the transcriptional activity by GR.