Diversified targets of FKBP25 and its complex with rapamycin

Int J Biol Macromol. 2014 Aug:69:344-52. doi: 10.1016/j.ijbiomac.2014.05.060. Epub 2014 May 29.

Abstract

FKBP25 is a member of the super-family of peptidylprolyl cis/trans isomerases, which is a high affinity binder for the immunosuppressive antibiotic rapamycin (Rpm). FKBP25 isolated from natural sources, its recombinant murine homologue (mFKBP25) and their complexes with rapamycin bind to diverse DNAs, RNAs and heparin affinity beads. The recombinant mFKBP25/rapamycin complex binds to several proteins including the calcineurin-A/calcineurin-B/calmodulin complex and to elongation factor 1β. We solved the X-ray structure of the C-terminal domain of mFKBP25 bound to rapamycin that has a higher resolution than of its human counterpart, and which clearly illustrates that the positively charged 40s loop is an epitope of the FK506-like binding domain (FKBD) for interactions with various biopolymers.

Keywords: FKBP; FKBP25; Immunophilin; PPIase; Rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA / metabolism
  • Genomics
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / metabolism
  • Sirolimus / metabolism*
  • Tacrolimus Binding Proteins / chemistry
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism*

Substances

  • Fkbp3 protein, mouse
  • RNA
  • DNA
  • Tacrolimus Binding Proteins
  • Sirolimus