Modulating amyloid self-assembly and fibril morphology with Zn(II).
Metal ions (Zn(II)) are demonstrated as probes of amyloid structure in simple segments of the Abeta peptide, Abeta(13-21). By restricting the possible metal binding sites to His13/His14 dyad, we show that Zn2+ can specifically control the rate of self-assembly and dramatically regulate amyloid morphology via distinct coordination environments as characterized by X-ray absorption spectroscopy. The data establish that the single His13 is sufficient to coordinate Zn2+ productively for typical amyloid fiber formation, while a distinct Zn2+ coordination environment can be accessed in the presence of His13/Hi14 dyad to stabilize sheet/sheet associations and the transition to a ribbon/tube morphology.
Center for the Analysis of SupraMolecular Self-assemblies, Department of Chemistry, Emory University, 1521 Dickey Drive, Atlanta, Georgia 30322, USA.
Jijun
J
Dong
Jacob E
JE
Shokes
Robert A
RA
Scott
David G
DG
Lynn
D000682:Amyloid / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002413:Cations, Divalent; D002942:Circular Dichroism; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D015032:Zinc / Q000737:chemistry*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D010446:Peptide Fragments; D015032:Zinc