High impact information on PPIF

• Our findings, thus, indicate that the expression of Apop-1 induces apoptosis though CypD-dependent pathway and that Apop-1 plays roles in cell death under physiological conditions [1].
• In conclusion, SlrA is a functional, cyclophilin-type PPIase and contributes to pneumococcal virulence in the first stage of infection, namely, colonization of the upper airways, most likely by modulating the biological function of important virulence proteins [2].
• Cyclosporin A-sensitive PPIase detected in the chloroplast was mostly localized to the thylakoids, which is suggestive of its function in the folding of membranal proteins [3].
• Cyclosporin A inhibited the activity largely localized to the mitochondrial matrix while rapamycin inhibited the PPIase activity associated with the mitochondrial membranes [3].
• Both hCyP2 and hCyP3 contain NH2-terminal hydrophobic extensions of 32 and 42 amino acids, respectively [4].

Biological context of PPIF

• The peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor (PPIF: previously known as cyclophilin 3) is a protein that is part of the mitochondrial permeability transition pore, the activation of which is involved in the induction of necrotic and apoptotic cell death [5].
• These two novel proteins, designated hCyP2 and hCyP3, share 65 and 76% amino acid sequence homology with hCyP1, respectively [4].
• In contrast to the results with hCyP1, Southern blot analysis indicated that both hCyP2 and hCyP3 gene sequences are represented infrequently in the human genome [4].
• Substrate specificity was examined with 11 synthetic peptides (Suc-Xaa-Yaa-Pro-Phe-4-nitroanilide), and inhibition of the peptidyl-prolyl isomerase activities associated with hCyP1, hCyP2, and hCyP3 was studied with CsA, MeAla6-CsA and MeBm2t1-CsA [4].
• Disruption of the parvulin family peptidyl prolyl isomerase (PPIase) Pin1 gene delays reentry into the cell cycle when quiescent primary mouse embryo fibroblasts are stimulated with serum [6].

Anatomical context of PPIF

• Protein-specific antibodies revealed the predominant association of hCyP2 and hCyP3 with membranes and subcellular organelles, which suggests that the amino-terminal leader sequences of the two CyP isoforms may act as signal peptides [4].
• TLP20 is suggested to be the major PPIase and protein folding catalyst in the thylakoid lumen of plant chloroplasts [7].
• To test this hypothesis, we have characterized the PTP of isogenic wild-type and CypD- mouse liver mitochondria in patch clamp experiments, which allow biophysical characterization [8].
• Mitochondria isolated from engineered mice lacking Cyclophilin D (CypD), a component of the Permeability Transition Pore (PTP) complex, can still undergo a Ca2 + -dependent but Cyclosporin A-insensitive permeabilization of the inner membrane [8].

Associations of PPIF with chemical compounds

• AIM: To investigate methods for identifying specific cyclophilin D (CypD) inhibitors derived from quinoxaline, thus developing possible lead compounds to inhibit mitochondrial permeability transition (MPT) pore opening [9].

Other interactions of PPIF

• Mutational analysis of ANX11, DLG5, and PPIF revealed no disease-associated mutations [10].

Analytical, diagnostic and therapeutic context of PPIF

• By site-directed mutagenesis of CyPD that compromises peptidyl-prolyl cis-trans isomerase (PPIase) activity, we demonstrate that the mechanism involved in this protective effect requires PPIase activity [11].
• METHODS: Kinetic analysis of the CypD/inhibitor interaction was quantitatively performed by using surface plasmon resonance (SPR) and fluorescence titration (FT) techniques [9].

References