Metal binding in amyloid beta-peptides shows intra- and inter-peptide coordination modes.
X-ray absorption spectroscopy data show different metal binding site structures in beta-amyloid peptides according to whether they are complexed with Cu(2+) or Zn(2+) ions. While the geometry around copper is stably consistent with an intra-peptide binding with three metal-coordinated Histidine residues, the zinc coordination mode depends on specific solution conditions. In particular, different sample preparations are seen to lead to different geometries around the absorber that are compatible with either an intra- or an inter-peptide coordination mode. This result reinforces the hypothesis that assigns different physiological roles to the two metals, with zinc favoring peptide aggregation and, as a consequence, plaque formation.
Stellato
Francesco
F
Dipartimento di Fisica, Università di Roma "Tor Vergata" INFM and INFN, Via della Ricerca Scientifica 1, 00133 Roma, Italy.
Menestrina
Gianfranco
G
Serra
Mauro Dalla
MD
Potrich
Cristina
C
Tomazzolli
Rossella
R
Meyer-Klaucke
Wolfram
W
Morante
Silvia
S
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002413:Cations, Divalent; D003300:Copper / Q000737:chemistry*; D005583:Fourier Analysis; D006639:Histidine / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013057:Spectrum Analysis / Q000379:methods; D014965:X-Rays; D015032:Zinc / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D007093:Imidazoles; D006639:Histidine; D003300:Copper; C029899:imidazole; D015032:Zinc