Abstract
The human Pin1 WW domain catalyzes the cis–trans isomerization of the proline peptide bond. In this study, the conformation and binding of Cu(II) ions by Pin1 were investigated. It has been found that the affinity of peptide fragments of the human Pin1 WW domain for Cu(II) ions depends on its conformation. In particular, we analyzed three peptides derived from human Pin1: the nonapeptide hPin1(14–22) (with sequence Arg-Met-Ser-Arg-Ser-Ser-Gly-Arg-Val-NH2, peptide 1) the undecapeptide hPin1(13–23) (with sequence Lys-Arg-Met-Ser-Arg-Ser-Ser-Gly-Arg-Val-Tyr-NH2, peptide 2) and its derivative Ala13Ala23hPin1(13–23) (with sequence Ala-Arg-Met-Ser-Arg-Ser-Ser-Gly-Arg-Val-Ala-NH2, peptide 3) to study the role of presence in the sequence of the flanked residues at the N- and C-terminus, i.e., Lys13 and Tyr23. The presence of heat-capacity peaks found by DSC measurements for the systems studied strongly suggests that the conformational equilibria of the peptides studied strongly depend on the temperature. NMR spectroscopy and molecular dynamics simulations were instrumental to verify the conformational preferences of three peptides. The absence of likely or oppositely charged groups at the ends of a short chain fragment destroys chain reversal because the charged groups probably screen the nonpolar core from the solvent. ITC experiment was used to study the interactions with Cu(II) ions. It was found that the most stable complexes with Cu2+ ions are formed with peptide 2, which has the most bent conformation.
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Abbreviations
- hPin1:
-
Human cell regulatory protein
- SPPS:
-
Solid-phase peptide synthesis
- DSC:
-
Differential scanning calorimetry
- C p :
-
Heat of capacity
- T m :
-
Melting temperature
- ITC:
-
Isothermal titration calorimetry
- Mes:
-
2-(N-morpholino)ethanesulfonic acid
- NMR:
-
Nuclear magnetic resonance
- TOCSY:
-
Two-dimensional nuclear magnetic resonance spectroscopy
- ROESY:
-
Rotating frame nuclear Overhauser effect spectroscopy
- DQF-COSY:
-
Double-quantum filtered correlation spectroscopy
- CD:
-
Circular dichroism
- MD:
-
Molecular dynamic simulation
- rmsd:
-
Root-mean-square deviation
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Acknowledgements
Calculations were carried out using the resources of the Informatics Center of the Metropolitan Academic Network (IC MAN) in Gdansk. Fondazione Ente Cassa di Risparmio di Firenze is greatly acknowledged for supporting Pept Lab of the University of Florence. Moreover, the Erasmus Program 2014 is acknowledged for the traineeship fellowship of DU in Pept Lab at the University of Florence.
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Uber, D., Wyrzykowski, D., Tiberi, C. et al. Conformation-dependent affinity of Cu(II) ions peptide complexes derived from the human Pin1 protein. J Therm Anal Calorim 127, 1431–1443 (2017). https://doi.org/10.1007/s10973-016-5387-9
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DOI: https://doi.org/10.1007/s10973-016-5387-9