FIG. 10.
(A) Normal assembly cycle. During cell-free assembly of PR complexes, an ordered pathway is followed. (1) Hsp70 and Hip bind at an early stage. (2) An intermediate complex containing Hsp70, Hop, and Hsp90 is formed. (3) The functionally mature complex contains Hsp90, p23, and any one of three immunophilins (Imph.). Hormone binding by PR is deficient (dashed outline of PR) until the mature complex is formed. The mature complex is not stable; if PR dissociates without binding hormone, it reenters the assembly cycle. (B) APAV2-arrested assembly. Hip mutant APAV2, or N-303, is permissive for Hsp70 binding and dissociation but prevents the coassociation of Hop-Hsp90 and Hsp70 on PR. (C) Hip-mediated transition in PR complexes. It is proposed that Hip normally facilitates binding of Hop to Hsp70 when Hsp70 is associated with PR, thus promoting progression of PR assembly to the intermediate complex containing Hsp90. The indirect association of Hsp90 with PR complexes may favor displacement of Hsp70 and direct binding of Hsp90 to PR.