Kinetic intermediates in the formation of the cytochrome c molten globule.
The relationship between molten globules and transient intermediates in protein folding has been explored by equilibrium and kinetic analysis of the compact acid-denatured A-state of cytochrome c. The chloride-induced formation of the A-state is a complex reaction with structural intermediates resembling those found under native refolding conditions, including a rapidly formed compact state and a subsequent intermediate with interacting N- and C-terminal helices. Together with mutational evidence for specific helix-helix packing interactions, this shows that the A-state is a stable analogue of a late folding intermediate. The L94A mutation blocks all folding steps after the initial collapse and its equilibrium state resembles early kinetic intermediates.
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Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Roder
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D000818:Animals; D003574:Cytochrome c Group / Q000737:chemistry*; D006736:Horses; D006358:Hot Temperature; D006851:Hydrochloric Acid / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D011189:Potassium Chloride / Q000494:pharmacology; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D017433:Protein Structure, Secondary
D003574:Cytochrome c Group; D011189:Potassium Chloride; D006851:Hydrochloric Acid