Proteins equilibrium clusters

Stradner, A., H. Sedgwick, F. Cardinaux, W. C. K. Poon, S. U. Egelhaaf, and P. Schnrtenberger. 2004. Equilibrium cluster formation in concentrated protein solutions and colloids. Nature. 432,492. 

A puzzling problem was posed by Levinthal many years ago.329 We usually assume that the peptide chain folds into one of the most stable conformations possible. However, proteins fold very rapidly. Even today, no computer would be able, in our lifetime, to find by systematic examination the thermodynamically most stable conformation.328 It would likewise be impossible for a folding protein to "try out" more than a tiny fraction of all possible conformations. Yet folded and unfolded proteins often appear to be in a thermodynamic equilibrium Experimental results indicate that denatured proteins are frequently in equilibrium with a compact denatured state or "molten globule" in which hydrophobic groups have become clustered and some secondary structures exists.330-336 From this state the polypeptide may rearrange more slowly through other folding intermediates to the final "native conformation."3363 3361 ... 

The existence of a transit pool of free iron , which would be in equilibrium with iron-containing proteins, is a thermodynamic necessity, but its size is probably extremely small in normal conditions. Microsomal membranes contain nonheme-iron which is released upon incubation with some intermediates of heme synthesis (reviewed in ref. [155]). The resulting free-iron pool does initiate lipid peroxidation in vitro. In the cytosol, the iron-transit pool would be composed of Fe(III) and/or Fe(II), complexed with low-molecular-weight chelators, possibly in the form of polynuclear clusters [149],... 

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