Zinc(II) binds to the neuroprotective peptide humanin

The abnormal accumulation of the peptide amyloid-beta in the form of senile (or amyloid) plaques is one of the hallmarks of Alzheimer’s disease (AD). Zinc ions have been implicated in AD and plaques formation. Recently, the peptide humanin has been discovered. Humanin showed neuroprotective activity against amyloid-beta insults. Here the question investigated is if humanin could interact directly with ZnII. It is shown that ZnII and its substitutes CdII/CoII bind to humanin via a thiolate bond from the side chain of the single cysteine at position 8. The low intensity of the d–d bands of CoII–humanin indicated an octahedral coordination geometry. Titration experiments suggest that ZnII binds to humanin with an apparent affinity in the low μM range. This apparent Zn-binding affinity is in the same order as for amyloid-beta and glutathione and could thus be of physiological relevance.