Proline residues cytochrome

Cytochrome c possesses three phyllogenetically-conserved proline residues that are presumably involved in the correct folding of the protein to form the native structure. The effects of substitutions at one of these sites, Pro-71 (Fig. 4), on the equilibrium and kinetics of yeast iso-2-cytochrome c unfolding have been studied by Nall and co-workers through comparison of the properties of a Thr... 

The fraction of Us molecules depends on the number of proline residues and on their isomeric state in the native protein. In particular, the presence of cts-prolyl peptide bonds in the folded molecules leads to a high fraction of Us, since in unfolded proteins the cis state is populated to a small extent only. Adler and Scheraga (1990) showed by NMR that in heat-unfolded RNase A the nonnative trans isomers predominate at both Pro93 and Proll4. The Up molecules dominate in the unfolded state of proteins that have only tram-prolyl peptide bonds, such as lysozyme (Kato et ai, 1981, 1982), cytochrome c (Ridge el ai, 1981 Nall,... 

Probably not all proline residues are important for protein folding. Evidence for nonessential prolines came from a comparison of several homologous pancreatic RNases (Krebs et al., 1983, 1985) and cytochromes c (Babul et ai, 1978 Nall, 1990) that differ in the number of proline residues. Such prolines could be nonessential because they do not interfere with folding, or, alternatively, because they remain nativelike as regards isomeric state, after unfolding. 

SH3 domains occur in signal proteins that are involved in Tyr kinase signaling pathways (review Macias et al., 2002). They are also found in proteins of the cytoskeleton and in a subunit of the neutrophilic cytochrome oxidase. Ligand binding at SH3 domains takes place via Pro-rich sequences of ca. 10 amino acids. The sequence X-P-p-X-P is a consensus sequence for SH3 ligands, in which the two proline residues P are invariant X is usually an aliphatic residue and p is often a Pro residue. The structural... 

Zheng, Y.-M., M.B. Fisher, N. Yokotani, Y. Fujii-Kuriyama, and A.E. Rettie (1998). Identification of a meander region proline residue critical for heme binding to cytochrome P450 Implications for the catalytic function of human CYP4B1. Biochemistry 37, 12847-12851. 

Figure 5 Consensus structured regions (CSRs) predicted by the analysis of families of homologous proteins (a) cytochrome c family (b) mammalian ribonuclease family. The CSRs are shown (in bold) as independent segments and are also highlighted on the ribbon drawing of the entire chain. The numbers indicate the residues delimiting the CSRs in the reference structures (cytochrome c2 and bovine ribonuclease. respectively). Proline residues are displayed in full atomic detail and highlighted in view of the effect that proline cis/trans isomerization could have on the formation of early-folding intermediates ...

Flo. 44. Schematic representation of amino acid chains of various types of eukaryotic and prokaryotic cytochromes c. Cytochromes are listed at the left beside the amino terminus of each chain. Figures at the right, by the carboxyl terminus, are rough numbers of amino acids per chain. C, H, M, and P are cysteine, histidine, methionine, and proline, and large dots represent unspecified amino acid residues between cysteines. The chain lengths as represented by horizontal lines are only approximate. Adapted from reference 36. ... 

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