Ca(2+)- and Al(3+)-induced conformational transitions of amyloid fragment H-Ile-Ile-Gly-Leu-Met-NH2.
The effect of Ca2+ and Al3+ binding on the conformation of the neurotoxic amyloid fragment H-Ile-Ile-Gly-Leu-Met-NH2 [betaA(31-35)NH2] was studied in trifluoroethanol solutions and in the presence of liposomes. Comparative circular dichroism and Fourier-transform infrared spectroscopic studies revealed that the peptide forms a specific 1:1 complex with Ca2+ which coordinates the polar amide carbonyl groups of the peptide backbone. The results suggest the importance of a folded structure in the complexation of Ca2+. On the contrary, the increasing Al3+ concentration causes a gradual shift of the conformational equilibrium toward beta-sheet structure reflecting no specific binding site for Al3+. In the presence of liposomes the peptide adopts a conformation similar to that of the Ca(2+)-peptide complex. The relevance of the stabilization of peptide conformation by Ca2+ and liposome binding to the bioactive conformation of betaA(31-35)NH2 is also discussed.
Institute of Biophysics, Biological Research Center, Szeged, Hungary.
I
I
Laczkó
E
E
Vass
K
K
Soós
J L
JL
Varga
S
S
Száraz
M
M
Hollósi
B
B
Penke
D000535:Aluminum / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000648:ultrastructure*; D002118:Calcium / Q000494:pharmacology*; D002942:Circular Dichroism; D006801:Humans; D009498:Neurotoxins / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments; D000535:Aluminum; D002118:Calcium