Peptidyl-prolyl cis-trans isomerase

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Function

Peptidyl-prolyl cis-trans isomerase (PPIase) interconverts cis and trans isomers of proline. PPIase functions as a protein folding chaperone.

  • PPIase Pin1 isomerizes phospho-serine/threonine proline motifs[1]. The deregulation of Pin1 may be involved in cancer and Alzheimer Disease. Pin1 consists of 2 domains: the WW domain recognizes the pSer/pThr Pro motif and the PPIase domain contains the catalytic site.
  • PPIase PinA is an archaeal parvulin-like PPIase.
  • PPIase Mip (macrophage infectivity potentiator) is required for optimal infection of macrophages by some parasites[2].
  • PPIase SlyD acts as a chaperone and speeds up protein folding.
  • PPIase SlpA is a 2-domain protein containing an FK506-binding domain and a PPIase domain and a small insert-in-flap domain which acts as a chaperone[3].

For various types of PPIase see:
• Cyclophilin
• FK506 binding protein for SlyD
• The Escherichia coli sensitive to lysis D (SlyD) protein
• Multifaceted SlyD from Helicobacter pylori: implication in NiFe hydrogenase maturation

Disease

Mutations in PPIase genes are associated with age-related diseases like cardiovascular diseases, atherosclerosis, diabetes type II, chronic kidney disease, neurodegredation, cancer and age-related macular degeneration[4].

Structural highlights

The phosphoserine containing peptide found in the heptad repeat of RNA polymerase II large subunit interacts with the WW domain of PPIase Pin1[5]. The phosphoserine containing peptide binding site. Water molecules are shown as red spheres.

3D Structures of peptidyl-prolyl cis-trans isomerase

Peptidyl-prolyl cis-trans isomerase 3D structures


Human PPIase (green) complex with phosphoserine containing peptide (magenta) (PDB code 1f8a).

Drag the structure with the mouse to rotate

References

  1. ↑ Guito J, Gavina A, Palmeri D, Lukac DM. The cellular peptidyl-prolyl cis/trans isomerase Pin1 regulates reactivation of Kaposi's sarcoma-associated herpesvirus from latency. J Virol. 2014 Jan;88(1):547-58. doi: 10.1128/JVI.02877-13. Epub 2013 Oct 30. PMID:24173213 doi:http://dx.doi.org/10.1128/JVI.02877-13
  2. ↑ Fischer G, Bang H, Ludwig B, Mann K, Hacker J. Mip protein of Legionella pneumophila exhibits peptidyl-prolyl-cis/trans isomerase (PPlase) activity. Mol Microbiol. 1992 May;6(10):1375-83. PMID:1379319
  3. ↑ Quistgaard EM, Nordlund P, Low C. High-resolution insights into binding of unfolded polypeptides by the PPIase chaperone SlpA. FASEB J. 2012 Jun 26. PMID:22735173 doi:10.1096/fj.12-208397
  4. ↑ McClements L, Annett S, Yakkundi A, Robson T. The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases. Curr Mol Pharmacol. 2015;9(2):165-79. PMID:25986561
  5. ↑ Westerman ST. Tasting instilled otologic drops is not a reliable test of eustachian tube function. Arch Otolaryngol Head Neck Surg. 2000 Aug;126(8):1042. PMID:10922246

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