1. Quaternary structure of proteins relates to the interactions between separate polypeptide chains within the protein. The word polypeptide refers to a polymer of amino acids. A protein may contain one or more polypeptides and is folded and may be covalently modified.
2. Hemoglobin (and many other proteins) have multiple polypeptide subunits. Interactions between the subunits include ionic interactions, hydrogen bonds, and hydrophobic interactions. Modification of the quaternary structure of a protein may have the same effects as modification of its tertiary structure - alteration of its function/activity.
3. The enzyme ribonuclease (RNase) is interesting in being very stable to heat and other things that denature/inactivate other proteins. (By the way, denaturation is a word that means the tertiary and/or quaternary structure of a protein is disrupted.). RNase has disulfide bonds that help it to remain resistant to denaturation. Heating it to 100 Celsius, which denatures most proteins does not denature RNase. Breaking the disulfide bonds of RNAse with a reagent like mercaptoethanol followed by heating to 100 Celsius to destroy hydrogen bonds (or treatment with urea) causes loss of activity. If one allows the hydrogen bonds to reform slowly, some of the enzyme's activity reappears, which indicates that the information necessary for proper folding is contained in the primary structure (amino acid sequence).
4. Disulfide bonds are important structural components of proteins. They form when the sulfhydryls of two cysteines are brought together in close proximity. Some chemicals, such as mercaptoethanol, can reduce the disulfides (between cysteine residues) in proteins to sulfhydryls. In the process of transferring electrons to the cysteines, the sulfhydryls of mercaptoethanol become converted to disulfides. Treatment of RNase with mercaptoethanol reduces RNAse's disulfides to sulfhydryls. Subsequent treatment of RNase with urea disrupts hydrogen bonds and allows the protein to be denatured.
5. Interestingly, removal of the mercaptoethanol and urea from the solution allows RNase to refold, reestablish the correct disulfide bonds, and regain activity. Clearly, the primary sequence of this protein is sufficient for it to be able to refold itself to the proper configuration.
6. Other forces besides disulfide bonds that help to stabilize tertiary structure of proteins include hydrogen bonds, metallic bonds, ionic bonds, and hydrophobic bonds.
7. Chemicals that can disrupt some of these forces include urea or guanidinium chloride (disrupts hydrogen bonds), protons (ionic bonds), and detergents (hydrophobic bonds). In addition, dithiothreitol (DTT) can break disulfide bonds and make sulfhydryls.
8. Proteins sometimes have amino acids in them that are chemically modified. Chemical modification of amino acids in proteins almost always occurs AFTER the protein is synthesized (also described as post-translational modification). Examples include hydroxyproline and hydroxylysine in collagen, gamma carboxyglutamate, and phosphoserine. Modification of the collagen residues allows for the triple helical structure of the protein and for the strands to be cross-linked (an important structural consideration).
9. Hemoglobin (and many other proteins) have multiple polypeptide subunits. Interactions between the subunits include disulfide bonds, ionic interactions, hydrogen bonds, hydrophilic, and hydrophobic interactions. Modification of the quaternary structure of a protein may have the same effects as modification of its tertiary structure - alteration of its function/activity.
10. Folding is necessary for proteins to assume their proper shape and function. The instructions for folding are all contained in the sequence of amino acids, but we do not yet understand how those instructions are carried out rapidly and efficiently. Levinthal's paradox illustrates the fact that folding is not a random event, but rather based on an ordered sequence of events arising from the chemistry of each group.
11. Proper folding of a protein is essential. Cells have complexes called Chaperonins that help some proteins to fold properly. Misfolding of proteins is implicated in diseases such as mad cow disease and Creutzfeld-Jacob disease in humans. The causative agent in these diseases is a "contagious" protein that is coded by the genome of each organism. When it doesn't fold properly, it helps induce other copies of the same protein to misfold as well, resulting in plaque-like structures that destroy nerve cells.
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