On the redox conformational change in cytochrome c.

Abstract

The relationship between the crystal structures of oxidized and reduced tuna cytochrome c has been reexamiined by a superposition method motivated by recent studies of the cytochrome c-cytochrome c peroxidase complex. It is shown that the observed structural changes precisely reflect the binding face suggested by chemical modification studies. It is further suggested that the large observed motion of Iysine-27 and a smaller overall motion of the two binding edges constitute a redox binding-affinity switch and that the driving force for the conformational change of the protein is provided by the internal conformational change and charge redistribution of the heme, which cause it to tilt, under the influence of covalent and nonbonded interactions, within its protein envelope. A picture is presented of the molecule as an electron storage/ transfer machine with three elements-a binding module, an electron storage module, and a conformational energy-storage module.The architecture of cytochrome c and the relationship of that structure to the molecule's role as an electron-transfer pro' tein have been a concern of molecular biologists for some time. The occurrence of variants of the molecule in the most diverse species has made it the classic subject for studies of molecular evolution. The fact that many of the cytochromes c can be crystallized has made it possible to consider this problem not only from the viewpoint of sequence homology but also to relate the observed features of sequence variation to the structure of the molecule.A problem of central interest is the comparison of the structures of the oxidized and reduced forms of the molecule and the unraveling of the relationship between any observed changes and the function of the molecule. In a classic series of papers (1-3), Dickerson and collaborators have elucidated the structures of the oxidized and reduced forms of tuna cytochrome c, and have compared the two forms by a superposition method. In these studies, in which superposition of all corresponding atoms of the protein (excluding the heme) was optimized, significant conformational changes were observed in the "bottom half' of the molecule, particularly in the region of residues 47-57. It was suggested that these changes, together with motions of the heme, constitute a mechanism for regulating the redox potential of the molecule. Recent calculations (4) also indicate that the protein environment lowers the apparent activation energy for electron transfer by the heme.Still another question which has been investigated extensively is the mode of binding of cytochrome c to its redox partners. Modification studies (5-7) have strongly supported the suggestion that a ring of lysine residues is responsible for proper binding of cytochrome c and that this binding occurs by an electrostatic mechanism. The lysines believed to be responsible are at positions 8, 13, 27, 72, 79, 86, and 87. Until recently, however, no crystallographic evidence was available for this hypothesis. Now, however, the structure of c...

Defining the Apoptotic Trigger

“…previous cytochrome c crystal structures (35,43) have shown that structural differences are partially localized to the binding site of cytochrome c for its BC1 binding partner (44); the results presented herein agree well with these studies.…”

Cytochrome c adducts with PCB quinoid metabolites

“…This may be caused by the oxidation of a hydroquinone or semiquinone adduct by the ferric heme group in cytochrome c resulting in reduced cytochrome c and a PCB quinone adduct. Lysine 27 was reported to surround the heme crevice (Geren & Millett 1981) and to interact with the heme group in cytochrome c (Rackovsky & Goldstein 1984). Thus the adduct formation of PCB3-pQ on lysine 27 may lead to an interaction with the heme group.…”

Viscosity Dependence of the Electron Transfer Rate from Bound Cytochromecto P840 in the Photosynthetic Reaction Center of the Green Sulfur BacteriumChlorobium tepidum,

“…The c-type cytochromes are known to undergo structural changes depending on the heme redox state (Rackovsky & Goldstein, 1984;Berghuis & Brayer, 1992). Conformational change or dehydration of cytochrome c induced by the high concentration of glycerol may affect the reaction rate.…”