How native-state topology affects the folding of dihydrofolate reductase and interleukin-1beta.
The overall structure of the transition-state and intermediate ensembles observed experimentally for dihydrofolate reductase and interleukin-1beta can be obtained by using simplified models that have almost no energetic frustration. The predictive power of these models suggests that, even for these very large proteins with completely different folding mechanisms and functions, real protein sequences are sufficiently well designed, and much of the structural heterogeneity observed in the intermediates and the transition-state ensembles is determined by topological effects.
Clementi
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Departments of Physics and Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA. cclementi@ucsd.edu
Jennings
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Onuchic
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D001426:Bacterial Proteins / Q000737:chemistry*; D003198:Computer Simulation; D004926:Escherichia coli / Q000201:enzymology; D007375:Interleukin-1 / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*; D013816:Thermodynamics
D001426:Bacterial Proteins; D007375:Interleukin-1; D013762:Tetrahydrofolate Dehydrogenase