Tentative scheme for thermal unfolding of holo- and apo- forms of CP based on our work (trapezoid indicates intact domain, and circle molten-globule-like domain). We propose that the first N-to-I transition involves unfolding of one or two domains, perhaps domain 2 as shown here. For holo-CP, the N-to-I step also couples to type-I copper release. One oxidized type-1 copper is lost (the one in domain 4 is shown, but it could also be the one in domain 6). If domain 2 is unfolded in I, it appears reasonable that the reduced type-1 copper in this domain is also lost (as shown here). This was previously concluded to be the case for the urea-induced CP intermediate (29). The last step involves destruction of the trinuclear copper cluster and structural perturbations in all domains.