Figure. The dimmer of FkpA complexed with FK506 (in red).
 

FkpA is a peptidyl-prolyl isomerase present in the periplasmic region of E. coli. The protein is divided into two domains: an N-terminal domain of unknown function and a C-terminal domain homologous to FKBP (or FK506-binding protein) which is able to bind the immuno-suppressor ligand FK506. FkpA is a heat-shock protein that catalyses certain steps in the folding of proteins.

We have determined the crystal structure of FkpA in three different forms: the complete molecule comprising 245 residues, FkpA truncated by 25 residues in the C-terminus, and truncated FkpA as a complex with FK506 (FK506 inhibits the isomerase function but not the chaperon activity). FkpA forms a dimer through the interlacing of helices in the N-terminal domain of the protein. In the structure of the complete molecule, the last 25 C-terminal residues are not visible, implying that they are disordered in the crystal. This observation lead us to produce a modified recombinant protein lacking these residues in order to improve crystal quality. The complex of truncated FkpA with FK506 shows the ligand to be bound in the same manner as in FKBP, an observation compatible with its isomerase function.We have also determined the structure of MalE31, a mutant of MalE (or Maltose-binding protein) from E. coli that forms inclusion bodies during expression owing to a defective folding. In the presence of FkpA, however, MalE31 is correctly folded, and the crystal structure of this mutant shows that its conformation is very close to that of the wild-type protein. This result is concordant with other observations that suggest that the misfolding of MalE31 is governed by kinetic factors.