Positive cooperativity in metal-templated dimerization is considered to be rare, while negative cooperativity characterizes many systems. The potential utility of the α-helical dHis motif for protein-protein interface nucleation by metal-binding was already well-known; however, the observation that cooperativity of templated dimerization is buffer modulated provides an additional handle for manipulation of the binding equilibrium. We serendipitously observed that in presence of phosphate buffer, Cu II -templated dimerization demonstrated apparent positive cooperativity, while in Tris-HCl buffer, this templated dimerization displayed strongly negative cooperativity behaviour.