3D structure of human FK506-binding protein 52: Implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex

doi:10.1073/pnas.0305969101

3D structure of human FK506-binding protein 52: Implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex

^*Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China; ^†National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China; and ^§Beijing Institute of Basic Medical Science, Beijing 100850, China

Edited by Timothy A. Springer, Harvard Medical School, Boston, MA (received for review September 17, 2003)

Abstract

FK506-binding protein 52 (FKBP52), which binds FK506 and possesses peptidylprolyl isomerase activity, is an important immunophilin involved in the heterocomplex of steroid receptors with heat-shock protein 90. Here we report the crystal structures of two overlapped fragments [N(1–260) and C(145–459)] of FKBP52 and the complex with a C-terminal pentapeptide from heat-shock protein 90. Based on the structures of these two overlapped fragments, the complete putative structure of FKBP52 can be defined. The structure of FKBP52 is composed of two consecutive FKBP domains, a tetratricopeptide repeat domain and a short helical domain beyond the final tetratricopeptide repeat motif. Key structural differences between FKBP52 and FKBP51, including the relative orientations of the four domains and some important residue substitutions, could account for the differential functions of FKBPs.

Footnotes

↵ ¶ To whom correspondence may be addressed. E-mail: raozh{at}xtal.tsinghua.edu.cn or shenbf{at}mx.cei.gov.cn.
↵ ‡ B.W. and P.L. contributed equally to this work.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: PPIase, peptidylprolyl isomerase; FKBP, FK506-binding protein; Hsp, heat-shock protein; Hop, Hsp70/90 organizing protein; Cyp40, cyclophilin 40; PP5, protein phosphatase 5; TPR, tetratricopeptide repeat; FK1, first FKBP domain of FKBPs; FK2, second FKBP domain of FKBPs.
Data deposition: The atomic coordinates and structure factors for N(1–260) (space group P2₁), C(145–459), and C(145–459)/MEEVD have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 1Q1C, 1P5Q, and 1QZ2, respectively).