Protein folding cooperativity

Fig. 9.1. Hypothetical general p-T phase diagram for two-state cooperative protein folding, according to (9.1). The stability decreases with increasing or decreasing temperature from the AS = 0 line and with increasing or decreasing pressure from the AV = 0 line. The shape of the ellipse depends very strongly on A a and ACp...

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Miranker, A., Dobson, C.M. Collapse and cooperativity in protein folding. Curr. Opin. Struct. Biol. 

Temperature-sensitive mutations usually arise from a single mutation s effect on the stability of the protein. Temperature-sensitive mutations make the protein just unstable enough to unfold when the normal temperature is raised a few degrees. At normal temperatures (usually 37°C), the protein folds and is stable and active. However, at a slightly higher temperature (usually 40 to 50°C) the protein denatures (melts) and becomes inactive. The reason proteins unfold over such a narrow temperature range is that the folding process is very cooperative—each interaction depends on other interactions that depend on other interactions. 

Lnqne, I., Leavitt, S.A., Freire, E. (2002) The linkage between protein folding and functional cooperativity two sides of the same coin Annu. Rev. Biophys. Biomol. Struct. 31, 235-256. 

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... 

Deuerling E, Schulze-Specking A, Tomoyasu A, Mogk A, Bukau B. Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 1999 400 693-696. 

Protein folding and unfolding is thus largely an "all or none"process that results horn a cooperative transition. For example, suppose that a protein is placed in conditions under which some part of the protein structure is thermodynamically unstable. As this part of the folded structure is disrupted, the interactions between it and the remainder of the protein will be lost. The loss of these interactions, in turn, will destabilize the remainder of the structure. Thus, conditions that lead to the disruption of any part of a protein structure are likely to unravel the protein completely. The structural properties of proteins provide a clear rationale for the cooperative transition. 

The amino acid sequence completely determines the three-dimensional structure and, hence, all other properties of a protein. Some proteins can be unfolded completely yet refold efficiently when placed under conditions in which the folded form of the protein is stable. The amino acid sequence of a protein is determined by the sequences of bases in a DNA molecule. This one-dimensional sequence information is extended into the three-dimensional world by the ability of proteins to fold spontaneously. Protein folding is a highly cooperative process structural intermediates between the unfolded and folded forms do not accumulate. 

Jewett A, Pande VS, Plaxco KW (2003) Cooperativity, smooth energy landscapes and the origins of topology-dependent protein folding rates. J Mol Biol 326 247-253... 

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