Fig. (2).

A working hypothesis. (A) Different cellular pools of Era might have different reactivity towards cadmium depending on the cysteine residues (marked with a stick). The cysteine residues may become unavailable for interaction with cadmium for instance by posttranslational modifications (PTM) or oxidation. When a total population of ERa is exposed to cadmium, the metal binds close the ligand binding pocket of unmodified ERa and prevents the formation of active conformation recognized by AF-2 interacting coactivators, but in the case of modified ERa (the diamond indicates modification of the cysteine residues) cadmium binds outside the ligand binding pocket and pulls the receptor towards the active conformation that allows interaction with co-activators. (B) In living cells, membrane-associated ERa and nuclear unmodified ERa could be examples of receptor pools with different reactivity towards cadmium. (From Peter Fechner, Pauliina Damdimopoulou, Günter Gauglitz, Biosensors Paving the Way to Understanding the Interaction between Cadmium and the Estrogen Receptor Alpha, Plos One, 2011, Open Access).