Evolution of Protein Structures
Part I
Part I. Homologous Proteins
Proteins that have similar function and similar AA sequence as well as 3D shape are called Homologous Proteins. Invariant AAs are involved in function or bonding critical to the protein's shape. Variable AAs are only parts of the protein's framework. Those on the surface can vary more than those in the interior where tight packing of the side chains creates demands on the size and shape of the AAs in order to fit together properly during folding.
For example, if we analyze the AA sequences of the same protein from different organisms we see which AA have changed during the course of evolution and those that have not. One well studied example is the electron carrying protein of mitochondria called Cytochrome c which has a bound heme-Fe so it has a red-orange color like hemoglobin.
Figure 3. Structural Model of Cytochrome c showing a few of its invariant amino acids.
Figure from Metzler, Biochemistry - copyright 1972 Academic Press
Since Cytochrome c appears to be required for survival of eukaryotic organisms, change in its amino acid sequence, which reflects change in its gene, can be used to measure change in species during evolution.
Figure 4. Phylogenetic Tree of Species based on the Amino Acid Sequence of Cytochrome c.
Figure from Voet, Biochemistry - copyright 1990 John Wiley & Sons
First, we find that all cytochrome c proteins from eukaryotic organisms have the same 3-D shape and they all bind heme-Fe in the same way and are found in mitochondria. However, while there are about 100 AAs in all these cytochrome c proteins, only about 30 of the AAs are exactly the same in all of them.
Figure 5. Amino Acid Sequence of Cytochrome c shown with the single letter code for AAs. The invariant AA residues are shown in bold, upper case letters; variable AA residues shown in lower case letters. Only 16 invariant key residues shown here.
These invariant AA are absolutely required for functionality of cytochrome c. In other words, for cytochrome c to fold into its unique shape in each organism and work properly in the cell, it must retain certain invariant AAs in its amino acid sequence during evolution. But this applies to only a limited number of the AA residues in Cytochrome c, namely about 30 amino acids.
The other 70 AAs can vary in only a limited way - that is a change in AA usually retains its chemical and functional character. For example:
Lys can change to Arg
Glu can change to Asp
Ala can change to Val
Val can change to Ile
These variable AA are in the general framework of the protein. Surface AA residues can vary more than those in the interior. Those in key positions involved in the functionality of the protein are more constrained and can not vary without disturbing the 3-D shape of the protein and therefore its functionality. This is illustrated below with another model of Cytochrome c, where key AA residues for functionality are identified by showing contacts with the heme-Fe which is the functional part of Cytochrome c.
Figure 6. Model of Cytochrome c showing the positions of invariant and variable AAs. Invariant AAs is shown by a full bold circle around its name, while highly conserved (almost invariant) are shown with partial circle. Variable AAs are not circled. Covalently linked Cys-16 and Cys-17 are shown linked to the heme and His-18 and Met-80 are shown as non-covalent ligands (electron-donating groups) to the heme-iron. Other residues in contact with the heme-iron have additional black spheres extending from their names.
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©Wilbur H. Campbell, 1995; wcampbel@mtu.edu