Metal Switch for Amyloid Formation:  Insight into the Structure of the Nucleus

The role of Zn2+ in pre-organizing Abeta(10-21) amyloid formation is shown to preferentially alter the relative rate of fibril nucleation and to have little influence on fibril propagation. Fibril morphology, as determined by small angle neutron scattering (SANS) and transmission electron microscopy (TEM), was unchanged in the presence and absence of Zn2+ in Abeta(10-21), as well as in a series of site-specifically altered variants. The metal-independence of the Abeta(10-21)H13Q peptide suggested that the increase in nucleation rate in Abeta(10-21) is due to Zn2+-mediated inter-sheet interactions, involving both histidine 13 and histidine 14.