Folding Barrier in Horse Cytochrome c: Support for a Classical Folding Pathway

Abstract

Native-state structures and conformations of ferrocytochrome c, nitrosylcytochrome c, and carbonmonoxycytochrome c are very similar. They are, however, immensely different from each other in terms of thermodynamic stability. The dramatic destabilization of ferrocytochrome c to the extent of 12kcalmol-1 produces no effect on the folding rate, and this is so in spite of the fact that all three test-tube variants fold in an apparent two-state manner. For all three proteins the folding barrier is early in time, sizable in energy, and is of the same magnitude (∼6.5kcalmol-1). These results raise some challenges to the "new view" of protein folding. An early transition state, the search for which consumes most of the observed folding time, is suggested. © 2004 Elsevier Ltd. All rights reserved.