Peptides Derived from Angiogenin Regulate Cellular Copper Uptake
The angiogenin protein (ANG) is one of the most potent endogenous angiogenic factors. In this work we characterized by means of potentiometric, spectroscopic and voltammetric techniques, the copper complex species formed with peptide fragments derived from the N-terminal domain of the protein, encom...
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doaj-71cec9573cc744cfb31141390ba3cf522021-09-09T13:48:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-01229530953010.3390/ijms22179530Peptides Derived from Angiogenin Regulate Cellular Copper UptakeGiovanni Tabbì0Lorena Maria Cucci1Calogero Pinzino2Alessia Munzone3Tiziano Marzo4Silvia Pizzanelli5Cristina Satriano6Antonio Magrì7Diego La Mendola8Institute of Crystallography—National Council of Research—CNR, via Paolo Gaifami 18, 95126 Catania, ItalyNano Hybrid BioInterfaces Lab (NHBIL), Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, ItalyInstitute for the Chemistry of OrganoMetallic Compounds (ICCOM), National Council of Research—CNR, via G. Moruzzi 1, 56124 Pisa, ItalyAix-Marseille Univesité, 52 Avenue Escadrille Normandie Niemen, 13013 Marseille, FranceDepartment of Pharmacy, University of Pisa, via Bonanno Pisano 6, 56126 Pisa, ItalyInstitute for the Chemistry of OrganoMetallic Compounds (ICCOM), National Council of Research—CNR, via G. Moruzzi 1, 56124 Pisa, ItalyNano Hybrid BioInterfaces Lab (NHBIL), Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, ItalyInstitute of Crystallography—National Council of Research—CNR, via Paolo Gaifami 18, 95126 Catania, ItalyDepartment of Pharmacy, University of Pisa, via Bonanno Pisano 6, 56126 Pisa, ItalyThe angiogenin protein (ANG) is one of the most potent endogenous angiogenic factors. In this work we characterized by means of potentiometric, spectroscopic and voltammetric techniques, the copper complex species formed with peptide fragments derived from the N-terminal domain of the protein, encompassing the sequence 1-17 and having free amino, Ang1-17, or acetylated N-terminus group, AcAng1-17, so to explore the role of amino group in metal binding and cellular copper uptake. The obtained data show that amino group is the main copper anchoring site for Ang1-17. The affinity constant values, metal coordination geometry and complexes redox-potentials strongly depend, for both peptides, on the number of copper equivalents added. Confocal laser scanning microscope analysis on neuroblastoma cells showed that in the presence of one equivalent of copper ion, the free amino Ang1-17 increases cellular copper uptake while the acetylated AcAng1-17 strongly decreases the intracellular metal level. The activity of peptides was also compared to that of the protein normally present in the plasma (wtANG) as well as to the recombinant form (rANG) most commonly used in literature experiments. The two protein isoforms bind copper ions but with a different coordination environment. Confocal laser scanning microscope data showed that the wtANG induces a strong increase in intracellular copper compared to control while the rANG decreases the copper signal inside cells. These data demonstrate the relevance of copper complexes’ geometry to modulate peptides’ activity and show that wtANG, normally present in the plasma, can affect cellular copper uptake.https://www.mdpi.com/1422-0067/22/17/9530electron spin resonancecopperangiogenesispeptideribonucleasesmetal complexes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giovanni Tabbì Lorena Maria Cucci Calogero Pinzino Alessia Munzone Tiziano Marzo Silvia Pizzanelli Cristina Satriano Antonio Magrì Diego La Mendola |
spellingShingle |
Giovanni Tabbì Lorena Maria Cucci Calogero Pinzino Alessia Munzone Tiziano Marzo Silvia Pizzanelli Cristina Satriano Antonio Magrì Diego La Mendola Peptides Derived from Angiogenin Regulate Cellular Copper Uptake International Journal of Molecular Sciences electron spin resonance copper angiogenesis peptide ribonucleases metal complexes |
author_facet |
Giovanni Tabbì Lorena Maria Cucci Calogero Pinzino Alessia Munzone Tiziano Marzo Silvia Pizzanelli Cristina Satriano Antonio Magrì Diego La Mendola |
author_sort |
Giovanni Tabbì |
title |
Peptides Derived from Angiogenin Regulate Cellular Copper Uptake |
title_short |
Peptides Derived from Angiogenin Regulate Cellular Copper Uptake |
title_full |
Peptides Derived from Angiogenin Regulate Cellular Copper Uptake |
title_fullStr |
Peptides Derived from Angiogenin Regulate Cellular Copper Uptake |
title_full_unstemmed |
Peptides Derived from Angiogenin Regulate Cellular Copper Uptake |
title_sort |
peptides derived from angiogenin regulate cellular copper uptake |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-09-01 |
description |
The angiogenin protein (ANG) is one of the most potent endogenous angiogenic factors. In this work we characterized by means of potentiometric, spectroscopic and voltammetric techniques, the copper complex species formed with peptide fragments derived from the N-terminal domain of the protein, encompassing the sequence 1-17 and having free amino, Ang1-17, or acetylated N-terminus group, AcAng1-17, so to explore the role of amino group in metal binding and cellular copper uptake. The obtained data show that amino group is the main copper anchoring site for Ang1-17. The affinity constant values, metal coordination geometry and complexes redox-potentials strongly depend, for both peptides, on the number of copper equivalents added. Confocal laser scanning microscope analysis on neuroblastoma cells showed that in the presence of one equivalent of copper ion, the free amino Ang1-17 increases cellular copper uptake while the acetylated AcAng1-17 strongly decreases the intracellular metal level. The activity of peptides was also compared to that of the protein normally present in the plasma (wtANG) as well as to the recombinant form (rANG) most commonly used in literature experiments. The two protein isoforms bind copper ions but with a different coordination environment. Confocal laser scanning microscope data showed that the wtANG induces a strong increase in intracellular copper compared to control while the rANG decreases the copper signal inside cells. These data demonstrate the relevance of copper complexes’ geometry to modulate peptides’ activity and show that wtANG, normally present in the plasma, can affect cellular copper uptake. |
topic |
electron spin resonance copper angiogenesis peptide ribonucleases metal complexes |
url |
https://www.mdpi.com/1422-0067/22/17/9530 |
work_keys_str_mv |
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