Archaeal peptidyl prolyl cis-trans isomerases (PPIases)

PPIases are ubiquitous in living organisms. While 3 families of PPIases, cy clophilin (CyP), FK506 binding protein (FKBP) and parvulin (Pvn), have been studied in detail in Eukarya and Bacteria (eubacteria), little is known ab out archaeal PPIases. Among 2 cyclophilins found in Archaea, only Halobacte rium cyclophilin (HcCyP19) has been characterized. It is a cyclosporin A (C sA) sensitive CyP with a MW of 19.4kDa. The PPIase activity and CsA sensiti vity of this CyP is higher at higher salt concentration in the medium. No p arvulin or its homolog has been found in Archaea. Two types of FKBPs, 26-30 kDa long type and 17-18 kDa short type FKBP, have been found in Archaea. Wh ile the N-terminal regions of these 2 type FKBPs are similar to each other, the long type archaeal FKBP has an additional ca. 100 amino-acid sequence at its C-terminal region. In comparison with human HsFKBP12, the N-terminal region of the archaeal FKBP has 2 insertion sequences in the regions corre sponding to Bulge and Flap of HsFKBP12. A short type archaeal FKBP from Met hanococcus thermolithotrophicus has been shown to have not only a PPIase ac tivity but also a chperone like activity, which includes protein refolding and aggregation suppressing activities with regard to protein folding inter mediates. Mutational analysis revealed that this chaperone-like activity wa s independent of the PPIase activity, and that the insertion sequence in th e region corresponding to the Flap seemed to be important.