alpha-Synuclein (alpha Syn) forms amyloid fibrils in the neurons of Parkinson's disease (PD) patients'. Despite a role for Cu2+ in accelerating alpha Syn fibril formation, coupled with reports of copper dishomeostasis in PD, there remain controversies surrounding the coordination geometry of Cu2+ with alpha Syn. Here we compare visible circular dichroism (CD) spectra of Cu2+ loaded on to full-length alpha Syn together with four peptides that model aspects of Cu2+ binding to the N-terminus and histidine50 of alpha Syn. With glycine as a competitive ligand, the affinity of Cu2+ for full-length alpha Syn is determined to have a conditional dissociation constant, at pH 7.4, of 0.1 nM. A similar affinity of 0.3 nM is determined for the tripeptide Met-Asp-Val(MDV) that mimics the N-terminus of alpha Syn, while the incorporation of a putative histidine side chain in the N-terminal complex facilitates the formation of a macrochelate with the histidine, which results in an increase in the affinity for Cu2+ to 0.03 nM at pH 7.4. Comparisons of the visible absorbance and CD spectra over a range of pH values also indicates that the MDV tripeptide closely models Cu2+ binding to full-length alpha Syn and rules out a role for His50 in the primary Cu2+ binding complex of monomeric alpha Syn. However, there are reports that suggest His50 does form a macrochelate with the N-terminal Cu2+ complex; we reconcile these conflicting observations by identifying a concentration dependence of the interaction. Only at the higher concentrations can the imidazole nitrogen bind to the N-terminal Cu2+ to form a ternary complex rather than via a macrochelate. This work shows even for this intrinsically disordered protein a large macrochelate with Cu2+ is not favored. Understanding Cu(2+ )coordination to alpha Syn gives a more complete picture of its place in amyloid assembly and cytotoxicity.