Principles of Protein Structure - G. Schultz 1982

Protein Evolution
Protein Differentiation
Cytochromes c

Cytochromes c arose through Protein Differentiation. As shown in Sect. 9.2, mitochondrial cytochromes c form a well-studied group of specialized Proteins. Other c-type cytochromes perform various Functions, most of which, however, involve electron attachment and transfer [509]. All cytochromes c can be viewed as a classic case of protein differentiation; yet, because the very term "cytochrome c" originated from spectral rather than structural Classification, any broad generalizations are currently unlikely. In addition to mitochondrial cytochrome c, X-Ray Structural Analysis has been completed for three bacterial cytochromes (Table 9.7) and initiated for three more prokaryotic cytochromes, namely cc₃, c₅₅₅, and c' [509].

Cytochromes c are subdivided into small and large variants. As analysis of three-dimensional structures and Amino acid sequences has shown, all known cytochromes c share the same chain folding pattern. However, large insertions and deletions have been found on their molecular surfaces, similar to those noted for protease B and Chymotrypsin (Fig. 9.4). Cytochromes c are categorized into small and large structural variants depending on the absence or presence of the 40–55 loop, respectively (Fig. 7.8).

Photosynthetic and respiratory cytochromes c are structurally as similar as Chymotrypsin and Trypsin. The classification of cytochromes c with known three-dimensional structures is given in Table 9.7. Among the members of the large variant, the Primary and secondary structures of cytochrome c from tuna Cell/35.html">Mitochondria, c₂ from Rhodospirillum rubrum, and c₅₅₀ from Paracoccus denitrificans (Table 9.7) show differences no greater than those observed between trypsin and chymotrypsin; thus, cytochromes c₂, c₅₅₀, and mitochondrial c can be considered evolutionarily related. Comparisons of these protein structures support the hypothesis [570] that mitochondria originated from Bacteria related to Paracoccus.

Attempts to determine the Amino Acid Sequence of c₅₅₁ (the small variant) based on the sequences of the large variants proved unsuccessful. Only through X-ray structural analysis of c₅₅₁ was the relationship between the two proteins revealed [571]. This X-Ray Diffraction study resolved ambiguities not only in establishing The amino acid sequence for this protein, but also for other cytochromes c with known sequences, such as the photosynthetic cytochromes c₆ (also referred to as f) of prokaryotic and eukaryotic Algae.

Class="center">Table 9.7 Small and large structural variants of c-type cytochromes^a

^a Data from [509].

Among the large variants, there are cytochromes that participate in electron transport during respiration, as well as those that form part of the photosynthetic Electron Transport Chain; the small variant exhibits this same functional diversity. This implies that both electron-transport chains may be closely related evolutionarily. This hypothesis is supported by the fact that respiration and photosynthesis are integrated at THE MOLECULAR LEVEL in Rhodopseudomonas spheroides, where a single cytochrome c₂ (a large variant) fulfills both functions [572]. To date, no Organism is known in which both functions are performed by the small variant.

Cystochnomes of type c can help elucidate the evolution of metabolic pathways. Cytochromes c introduce us to the vast realm of prokaryotes. In principle, the structures of these Proteins can be used to establish a definitive Taxonomy among bacteria, much like mitochondrial cytochromes c have been applied for taxonomic purposes in eukaryotic organisms. Initial attempts at such bacterial classification have already been made [509, 571]. However, because intergeneric Gene transfer can occur in bacteria [507, 508], the construction of a Phylogenetic Tree is complicated by genes that migrate from one Lineage to another.

Nevertheless, despite this phenomenon, it is suggested that c-type cytochromes can help trace The Development of modern photosynthesis and respiration from more ancient precursors (e.g., H₂S-based photosynthesis, sulfate-based respiration, etc.); they can contribute to explaining the evolution of metabolic pathways [571], which is one of the ultimate goals of research into protein differentiation [573, 574].