Evolution of Protein Structures
Introduction
Introduction
We have discussed secondary structure forms -- alpha-helix and beta-sheet -- and long distance interactions of AA side chains involved in causing the protein to fold into a certain shape as illustrated below:
Figure 1. The Four Levels of Protein Structure.
From unknown source who owns the copyright.
But what is the importance of the different shapes of proteins to their functions and
how limited is a particular protein's Amino Acid sequence over evolutionary time?
First, we should recall that the order of the amino acids in the backbone of a protein determine the shape it will fold into.
Primary Structure Determines Tertiary Structure
This was first demonstrated by Anfinsen (a scientist at the National Institutes of Health) when he denatured ribonuclease, an enzyme with 124 amino acids in its primary structure, by reducing its disulfide bonds and dialyzing it in 8M urea (a protein denaturing chemical). Once ribonuclease was denatured, it lost all its enzyme activity and had the properties of a linear polymer. Then when the urea and thiol reductant were removed, ribonuclease refolded into its native shape as demonstrated by the presence of its catalytic activity for degrading RNA.
Figure 2. Process of denaturing ribonuclease is reversible: denaturation takes place in the presence of the thiol reductant and urea; when these agents are removed the ribonuclease refolds into its native shape and regains its enzymatic activity.
Figure from Zubay et al., Principles of Biochemistry copyright 1995 Wm. C. Brown Comm., Inc.
Looking at individual AAs in the sequence of a family of the same type of protein we find that some of the amino acids can change while others must always be the same ones. For example, if we compared the amino acid sequences of ribonuclease from different organisms, we would find most of the amino acids are the same but a few have changed. However, if we compared the 3-D shape of the family of ribonucleases we would find no difference. Thus, the amino acids which changed during the evolution of ribonuclease did not change its 3-D shape or conformation. Ribonuclease remained the same enzyme over evolutionary time while its amino acid sequence changed based on changes in the DNA which encodes it.
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©Wilbur H. Campbell, 1995; wcampbel@mtu.edu