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

Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8348-53. doi: 10.1073/pnas.0305969101. Epub 2004 May 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Hydrogen Bonding
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary*
  • Receptors, Glucocorticoid / chemistry*
  • Receptors, Glucocorticoid / metabolism
  • Sequence Alignment
  • Tacrolimus Binding Proteins / chemistry*
  • Tacrolimus Binding Proteins / metabolism

Substances

  • HSP90 Heat-Shock Proteins
  • Macromolecular Substances
  • Receptors, Glucocorticoid
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 4
  • tacrolimus binding protein 5

Associated data

  • PDB/1P5Q
  • PDB/1Q1C
  • PDB/1QZ2