Toward a better understanding of protein folding pathways.
AUTOR(ES)
Creighton, T E
RESUMO
Experimental observations of how unfolded proteins refold to their native three-dimensional structures contrast with many popular theories of protein folding mechanisms. The available experimental evidence (ignoring slow cis-trans peptide bond isomerization) is largely consistent with the following general scheme: under folding conditions, unfolded protein molecules rapidly equilibrate between different conformations prior to complete refolding. This rapid prefolding equilibrium favors certain compact conformations that have somewhat lower free energies than the other unfolded conformations. Some of the favored conformations are important for productive folding. The rate-limiting step occurs late in the pathway and involves a high-energy, distorted form of the native conformation; there appears to be a single transition state through which essentially all molecules refold. Consequently, proteins are not assembled via a large number of independent pathways, nor is folding initiated by a nucleation event in the unfolded protein followed by rapid growth of the folded structure. The known folding pathways involving disulfide bond formation follow the same general principles. An exceptional folding mechanism for reduced ribonuclease A proposed by Scheraga et al. (Scheraga, H.A., Konishi, Y., Rothwarf, D.M. & Mui, P.W. (1987) Proc. Natl. Acad. Sci. USA 84, 5740-5744) is shown to result from experimental shortcomings, an incorrect kinetic analysis, and a failure to consider the kinetics of unfolding.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=281692Documentos Relacionados
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