With a combination of complementary experimental techniques, namely sedimentation assay, Fourier transform infrared spectroscopy, and x-ray absorption spectroscopy, we are able to determine the atomic structure around the metal-binding site in samples where amyloid- (A) peptides are complexed with either Cu(II) or Zn(II). Exploiting information obtained on a selected set of fragments of theA peptide, we identify along the sequence the histidine residues coordinated to the metal in the various peptides we have studied (A1–40,A1–16,A1–28,A5–23, and A17–40). Our data can be consistently interpreted assuming that all of the peptides encompassing the minimal 1–16 amino acidic sequence display a copper coordination mode that involves three histidines (His6, His13, and His14). In zinc-A complexes, despite the fact that the metal coordination appears to be more sensitive to solution condition and shows a less rigid geometry around the binding site, a four-histidine coordination mode is seen to be preferred. Lacking a fourth histidine along the A peptide sequence, this geometrical arrangement hints at a Zn(II)-promoted interpeptide aggregation mode.

Identifying the Minimal Copper- and Zinc-binding Site Sequence in Amyloid-beta Peptides

Dalla Serra, Mauro;Potrich, Cristina;
2008

Abstract

With a combination of complementary experimental techniques, namely sedimentation assay, Fourier transform infrared spectroscopy, and x-ray absorption spectroscopy, we are able to determine the atomic structure around the metal-binding site in samples where amyloid- (A) peptides are complexed with either Cu(II) or Zn(II). Exploiting information obtained on a selected set of fragments of theA peptide, we identify along the sequence the histidine residues coordinated to the metal in the various peptides we have studied (A1–40,A1–16,A1–28,A5–23, and A17–40). Our data can be consistently interpreted assuming that all of the peptides encompassing the minimal 1–16 amino acidic sequence display a copper coordination mode that involves three histidines (His6, His13, and His14). In zinc-A complexes, despite the fact that the metal coordination appears to be more sensitive to solution condition and shows a less rigid geometry around the binding site, a four-histidine coordination mode is seen to be preferred. Lacking a fourth histidine along the A peptide sequence, this geometrical arrangement hints at a Zn(II)-promoted interpeptide aggregation mode.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11582/5086
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
social impact