Highlights Protein Structure 3

1. Tertiary structure relates to interactions between amino acids in a protein that are not close in primary sequence. These interactions are made possible by folding to the protein chain to bring the distant amino acids closer together.

2. Tertiary structure is stabilized by disulfide bonds, ionic interactions, hydrogen bonds, hydrophilic, and hydrophobic interactions. Disulfide bonds are the strongest forces holding tertiary structure together, as they are covalent bonds.

3. Most proteins that are in cells are globular in nature.

4. Myoglobin is protein that acts as an oxygen 'battery', storing oxygen in muscles for when it is needed. Myoglobin contains a heme group that contains iron. Heme is a 'prosthetic group', which refers to a non-amino acid containing group that binds to a protein and augments its function.

5. Amino acid residues in myoglobin are arranged such that hydrophilic (and what your book calls ionic) amino acids are arranged on the outside and hydrophobic amino acids are largely arranged on the inside.

6. Porin is a membrane protein. Proteins embedded in membranes often have external amino acids that are hydrophobic so they can interact with the non-polar ortions of membranes. Porin, in addition, has a hole in the center that allows water to pass through it. The amino acids in porin are arranged with non-polars outside and polars inside.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. Misfolding is a problem in some diseases. Mad cow disease, scrapie (in sheep), and Creutzfeld-Jacob syndrome in humans all arise as a result of protein folding gone wrong. Cells have protein complexes called Chaperonins that help proteins to fold properly and avoid the misfolding problems.