We report the interaction of divalent Cd, Hg, and Pb cations with proteins of photosystem II (PSII) enriched membranes, in dried film with metal ion concentrations of 0.01, 0.1, 1, 5, 10, and 20 mM. Fourier transform infrared (FTIR) difference spectroscopy with self-deconvolution and second-derivative resolution enhancement measurements were used to determine the nature of the metal-protein interaction, the protein conformational transition, and the structural variations, upon metal complex formation. The infrared difference spectroscopic results revealed the presence of protein aggregation at low metal ion concentration (0.01 mM) with no major metal-protein interaction. At higher cation concentrations (1 to 20 mM), metal-protein binding was observed through peptide C=O and C-N groups with the participation of tyrosine residues. In addition, a major metal-sulfur binding was observed for the Hg ion but not for the Cd or Pb cation. Major conformational transitions from those of the mainly alpha-helix (64%) and beta-sheet (10%), in the uncomplexed proteins to alpha-helix (55-40%) and beta-sheet (10-20%), were observed in the presence of high cation concentration.