Identifying the minimal copper- and zinc-binding site sequence in amyloid-beta peptides.
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-beta (Abeta) peptides are complexed with either Cu(II) or Zn(II). Exploiting information obtained on a selected set of fragments of the Abeta peptide, we identify along the sequence the histidine residues coordinated to the metal in the various peptides we have studied (Abeta(1-40), Abeta(1-16), Abeta(1-28), Abeta(5-23), and Abeta(17-40)). 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 (His(6), His(13), and His(14)). In zinc-Abeta 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 Abeta peptide sequence, this geometrical arrangement hints at a Zn(II)-promoted interpeptide aggregation mode.
Minicozzi
Velia
V
Dipartimento di Fisica, Università di Roma Tor Vergata and Istituto Nazionale di Fisica Nucleare, Via della Ricerca Scientifica 1, I-00133 Roma, Italy.
Stellato
Francesco
F
Comai
Massimiliano
M
Dalla Serra
Mauro
M
Potrich
Cristina
C
Meyer-Klaucke
Wolfram
W
Morante
Silvia
S
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008670:Metals / Q000737:chemistry; D008954:Models, Biological; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared; D015032:Zinc / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D008670:Metals; D010455:Peptides; D006639:Histidine; D003300:Copper; D015032:Zinc