Helix movements and the reconstruction of the haem pocket during the evolution of the cytochrome c family

Analysis of cytochromes c (tuna), c₂ (Rhodospirillum rubrum), c₅₅₀ (Paracoccus denitrificans) and c₅₅₁ (Pseudomonas aeruginosa) shows that they contain 48 residues identifiable as homologous from superposition of the structures. The other 34 to 64 residues are in loops that vary greatly in sequence, length and conformation, or in α-helices that are found in only some of the structures. Of the 48 homologous residues, 17 are in three segments which pack onto the haem faces. In all four structures, these segments have the same conformations, and the same locations relative to the haem. The other 31 residues are in three α-helices which are in contact with each other. These form the back and one side of the haem pocket. In cytochrome c₅₅₁ the positions of the three α-helices have shifted and rotated, in comparison with cytochromes c and c₂, by up to 5 Å and 25 ° relative to the haem. These shifts, facilitated by mutations at the helix-helix interfaces, are related to the reconstruction of the propionic acid side of the haem pocket described by Almassy & Dickerson (1978). Together these effects produce alternative structures for the haem pocket. This mechanism of adaptation to mutation contrasts with that observed in the globins. In the globins, mutations also produce changes in helix interfaces and shifts of packed helices, but in the globins these shifts are coupled to conserve the structure of the haem pocket.