Cooperativity of protein folding

Preliminary Examination of the Origin of the Cooperativity of Protein Folding... 

Murphy KP, Bhakuni V, Xie D, Freire E (1992) Molecular basis of cooperativity in protein folding. III. Structural identification of cooperative folding units and folding intermediates, J Mol Biol, 227 293-306... 

Chemistry and Chemical Reactivity of Proteins, Matthew Francis Energetics of Protein Folding, Robert Baldwin NMR to Study Proteins, Angela Gronenborn Physical Chemistry in Biology, Allan Cooper... 

Many-Body Picture of Protein Folding Cooperativity and Wrapping... 

Thermodynamic stability is a global property of the enzyme structure, and contributions of individual amino acids toward the free energy of folding are additive and highly cooperative. Analysis of mutant proteins has defined the contributions of various amino acids toward the overall stability of the protein. Replacements which alter the formation of ion pairs, hydrogen bonds, van der Waals contacts, or hydrophobic interactions each tend to destabilize the folded protein by a qualitatively comparable amount (14). In one approach to this problem, site-specific substitution of amino acids has provided new approaches toward dissecting the kinetic mechanisms of protein folding (27). 

C. Origin of Cooperativity in Protein Folding and Two-State Thermodynamic Behavior in Protein Folding... 

All these studies seem to indicate that the cooperativity of the folding process is due to the specific pattern of tertiary interactions and/or the specific interplay between short- and long-range interactions. This may appear to be a trivial statement, but detailed analysis of the results from the simple, exact model, protein-like models and reduced models of real proteins show several specific requirements for the protein folding cooperativity. It is very encouraging that over the entire spectrum of theoretical model studies of the protein folding process, these requirements essentially overlap [35-37,51,83,92,95]. Naturally, various models place different stress on the specific interactions that may control protein folding and structural uniqueness. 

A. Cooper, Heat capacity of hydrogen-bonded networks an alternative vievt> of protein folding thermodynamics, in Biophys. Chem., 2000, 85, 25-39. 

Experimentally, to a very good approximation, many proteins exhibit a highly cooperative conformational transition that is well described by a two state model. Furthermore, in a number of proteins, the cooperativity in protein folding arises on passage from the molten globule state to the native... 

It is clear that the kinetics of protein folding is protein dependent. Some fold in a distinctly cooperative fashion, such that one can detect only the unfolded and native end states (U oN), being two-state in a kinetic as well as equilibrium sense. This is equivalent to saying that there is a single rate-limiting step, and intermediate species are not populated. Alternatively, some proteins fold by populating one or more distinct intermediate species (e.g., (7 -o- / -o- A see Eig. 2). Thus, formation of the intermediate species is fast, often formed in the dead-time of the instrument, and formation of the native species from the intermediate is relatively slow and easily monitored experimentally. It has been shown that this slow phase in some cases may be due to proline isomerization. ... 

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