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 Zn(II). It is shown that Zn(II) and its substitutes Cd(II)/Co(II) 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 Co(II)-humanin indicated an octahedral coordination geometry. Titration experiments suggest that Zn(II) binds to humanin with an apparent affinity in the low muM range. This apparent Zn-binding affinity is in the same order as for amyloid-beta and glutathione and could thus be of physiological relevance.
Armas
Ambar
A
Laboratoire de Chimie de Coordination, CNRS UPR 8241, University Toulouse, 205, route de Narbonne, F-31077 Toulouse Cedex, France.
Sonois
Vanessa
V
Mothes
Emmanuelle
E
Mazarguil
Honoré
H
Faller
Peter
P
D000042:Absorption; D000595:Amino Acid Sequence; D002104:Cadmium / Q000378:metabolism; D003035:Cobalt / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; C427211:humanin; D002104:Cadmium; D003035:Cobalt; D005978:Glutathione; D015032:Zinc