As targeted proteins that move within the cell, the steroid receptors have become very useful probes for understanding the linked phenomena of protein folding and transport. From the study of steroid receptor-associated proteins it has become clear over the past two years that these receptors are bound to a multiprotein complex containing at least two heat shock proteins, hsp90 and hsp56. Attachment of receptors to this complex in a cell-free system appears to require the protein unfolding/foIding activity of a third heat shock protein, hsp70. Like the oncogenic tyrosine kinase pp60Src, steroid receptors bind to this complex of chaperone proteins at the time of their translation. Binding of the receptor to the hsp90 component of the system occurs through the hormone binding domain and is under strict hormonal control. The hormone binding domain of the receptor acts as a transferable regulatory unit that confers both tight hormonal control and hsp90 binding onto chimaeric proteins. The model of folding and transport being developed for steroid receptors leads to some general suggestions regarding the folding and transport of targeted proteins in the cell.
Receptor Transformation and hsp90 Binding
The early studies of steroid receptor structure demonstrated that receptors could be recovered from hormone-free cells in two forms as defined by their behavior on sucrose gradient centrifugation. The small 4s form in cytosol was found to be a monomer (or in some cases a homodimer) that bound with high affinity to DNA and was formed at the expense of a larger 9s form without DNA binding activity. If cells were