Fig. 7: Conserved dual mechanism of cis-/trans-isomerization catalysis and molecular chaperone-like holding activity.
From: Catalysis of proline isomerization and molecular chaperone activity in a tug-of-war
a 3D structures of the three cyclophilins CypA (PDB code: 6I42), CypE (PDB code: 3UCH), and Cyp40 (PDB code: 1IIP). b Active site of CypA in complex with a peptide from the PreNAC region of aSyn (PDB code: 6I42). aSyn peptide residues labeled in blue. CypA residues of the active site are represented in yellow (conserved among CypA, CypE, and Cyp40), orange (residues mutated only in CypE or Cyp40), or red (residues not conserved among the three proteins). c Residue-specific intensity changes induced in aSyn in the presence of a 5-fold excess of CypA (top), CypE (middle), and Cyp40 (bottom). I0 and I are the intensities of 1H–15N HSQC cross-peaks in the absence and presence of enzymes, respectively. The domain organization of aSyn and the location of proline residues is shown on top. d Schematic representation of the tug-of-war between catalysis of proline isomerization and molecular chaperone activity: PPIase-catalyzed cis-/trans-isomerization lowers the energy barrier, which IDPs have to overcome during misfolding, while the chaperone-like holding activity of PPIases opposes aggregation.
