Repozytorium

The role of His-50 of α-synuclein in binding Cu(II): pH dependence, speciation, thermodynamics and structure.

Autorzy

Daniela Valensin

Francesca Camponeschi

Marek Łuczkowski

M. C. Baratto

Maurizio Remelli

Gianni Valensin

Henryk Kozłowski

Rok wydania

2011

Czasopismo

Metallomics

Numer woluminu

3

Strony

292-302

DOI

10.1039/C0MT00068J

Kolekcja

Naukowa

Język

Angielski

Typ publikacji

Artykuł

Streszczenie

Copper interaction with alpha synuclein (αS) has been shown to accelerate aggregation and oligomerization of the protein. Three different αS copper binding domains have been proposed: (i) the N-terminal residues (1–9) that represent the minimal copper binding domain; (ii) the His-50 imidazole and (iii) the Asp and Glu residues within the acidic C-terminal domain. The copper coordination at the N-terminus has been extensively characterized and it is generally accepted that it provides the highest affinity site. The same does not hold for the role played by His-50 in copper binding. In this work Cu(II) coordination to peptide fragments encompassing residues 45–55 of αS has been exhaustively characterized, including systems containing the inherited mutations E46K and A53T, as model peptides of the His-50 site. Through potentiometric titrations all the speciation profiles have been determined and the stability constants have been used to estimate the dissociation constants of complexes corresponding to the binding modes at pH 6.5 and 7.5. Spectroscopic analyses allowed determination of (i) the copper coordination sphere, (ii) its geometry and (iii) the constraints wherefrom the 3D structural models of the copper complexes could be obtained.

Adres publiczny

https://doi.org/ 10.1039/C0MT00068J

Strona internetowa wydawcy

https://global.oup.com/?cc=pl

Strona internetowa wydawcy

https://www.rsc.org/

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