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Conformation-dependent affinity of Cu(II) ions peptide complexes derived from the human Pin1 protein

ITC and DSC study

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Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

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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Authors and Affiliations

  1. Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland

    Dorota Uber, Dariusz Wyrzykowski, Lech Chmurzyński & Joanna Makowska

  2. Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Dipartimento di Chimica ‘Ugo Schiff’, University of Florence, Via Della Lastruccia 13, 50019, Sesto Fiorentino, Italy

    Caterina Tiberi, Giuseppina Sabatino & Anna Maria Papini

  3. PeptLab@UCPc/o Laboratory of Chemical Biology, University of Cergy-Pontoise, 5 Mail Gay-Lussac, 95031, Cergy-Pontoise, France

    Caterina Tiberi, Giuseppina Sabatino & Anna Maria Papini

  4. Laboratory of Biopolymer Structure, Intercollegiate Faculty of Biotechnology, University of Gdańsk - Medical University of Gdańsk, Kładki 24, 80-822, Gdańsk, Poland

    Wioletta Żmudzińska

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  1. Dorota Uber
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  2. Dariusz Wyrzykowski
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Correspondence to Joanna Makowska.

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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

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