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Journal of Thermal Analysis and Calorimetry

, Volume 127, Issue 2, pp 1431–1443 | Cite as

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

ITC and DSC study
  • Dorota Uber
  • Dariusz Wyrzykowski
  • Caterina Tiberi
  • Giuseppina Sabatino
  • Wioletta Żmudzińska
  • Lech Chmurzyński
  • Anna Maria Papini
  • Joanna Makowska
Article

Abstract

The human Pin1 WW domain catalyzes the cistrans 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.

Keywords

Peptide conformation β-Hairpin hPin1 peptides NMR 

Abbreviations

hPin1

Human cell regulatory protein

SPPS

Solid-phase peptide synthesis

DSC

Differential scanning calorimetry

Cp

Heat of capacity

Tm

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

Notes

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.

Supplementary material

10973_2016_5387_MOESM1_ESM.docx (861 kb)
Supplementary material 1 (DOCX 860 kb)

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Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2016

Authors and Affiliations

  • Dorota Uber
    • 1
  • Dariusz Wyrzykowski
    • 1
  • Caterina Tiberi
    • 2
    • 3
  • Giuseppina Sabatino
    • 2
    • 3
  • Wioletta Żmudzińska
    • 4
  • Lech Chmurzyński
    • 1
  • Anna Maria Papini
    • 2
    • 3
  • Joanna Makowska
    • 1
  1. 1.Faculty of ChemistryUniversity of GdańskGdańskPoland
  2. 2.Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Dipartimento di Chimica ‘Ugo Schiff’University of FlorenceSesto FiorentinoItaly
  3. 3.PeptLab@UCPc/o Laboratory of Chemical BiologyUniversity of Cergy-PontoiseCergy-PontoiseFrance
  4. 4.Laboratory of Biopolymer Structure, Intercollegiate Faculty of BiotechnologyUniversity of Gdańsk - Medical University of GdańskGdańskPoland

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