Mr D Eve

Marlborough School Science Department

Protein Structure
Tertiary and Quaternary Structure

Tertiary and Quaternary Structure
Lesson Objectives • To appreciate the importance of the tertiary protein structure and describe the types of bonding that maintain it. • To describe the quaternary structure of proteins, for example: haemoglobin including the role of Fe2+
Mr D Eve

Marlborough School Science Department

Telephone Wires
Telephone wires have a secondary structure similar to an alpha helix

They also have a tertiary structure!

Mr D Eve

Marlborough School Science Department

Myoglobin
The tertiary structure for myoglobin is fairly well understood and is shown here. Myoglobin has an alpha helix which then can be viewed as being enclosed in this blue sheath, the sheath doesn't exist but we can draw it that way. That helix folds back upon itself into what's referred to as the tertiary structure of myoglobin. Bonds between the side groups of the amino acid residues are responsible for holding together the tertiary structure of this protein.
Mr D Eve

Marlborough School Science Department

What bonds?
The kinds of bonds that can exist between the side groups include: • Van der Waals bonds (Hydrophobic) if the side groups are nonpolar. • Hydrogen bonds if the side groups contain hydroxyl or amino groups. • Ionic bonds if the side groups are acids and bases that can transfer protons from one to another making a carboxylate ion, which is negative, and essentially an ammonium or quaternary ammonium ion which is positive. • Covalent bonds if the side groups are cysteine residues in which the sulfur atoms are bonded together by the removal of two hydrogen atoms.
Mr D Eve

Marlborough School Science Department

Disulphide bridges
Disulfide bonds are formed by oxidation of the sulfhydryl groups on cysteine. Different protein chains or loops within a single chain are held together by the strong covalent disulfide bonds. Both of these examples are exhibited by the insulin in the graphic on the left.

Mr D Eve

Marlborough School Science Department

Hydrogen Bonding
Hydrogen bonding between "side chains" occurs in a variety of circumstances. The most usual cases are between two alcohols, an alcohol and an acid, two acids, or an alcohol and an amine or amide. In giving the structures for various examples, the backbone of the protein fragment will be represented by a short helix with only the side chain structure given as in the graphic on the left. In the prion protein, tyr 128 is hydrogen bonded to asp 178, which cause one part of the chain to be bonding with a part some distance away.
Mr D Eve

Marlborough School Science Department

Ionic Bonding
Salt bridges result from the neutralization of an acid and amine on side chains. The final interaction is ionic between the positive ammonium group and the negative acid group. Any combination of the various acidic or amine amino acid side chains will have this effect. The example on the left is from the prion protein with the salt bridge of glutamic acid 200 and lysine 204. In this case a very small loop is made because there are only three other amino acids between them. This salt bridge has the effect of straightening an alpha helix.
Mr D Eve

Marlborough School Science Department

Hydrophobic Interactions
The hydrophobic interactions of nonpolar side chains are believed to contribute significantly to the stabilizing of the tertiary structures in proteins. This interaction is really just an application of the solubility rule that "likes dissolve likes". The non-polar groups mutually repel water and other polar groups and results in a net attraction of the non-polar groups for each other. Hydrocarbon alkyl groups on ala, val, leu, and ile interact in this way. In addition, benzene (aromatic) rings on phe and tyr can "stack" together. In many cases this results in the nonpolar side chains of amino acids being on the inside of a globular protein, while the outside of the proteins contains mainly polar groups. Mr D Eve

Marlborough School Science Department

Examples of the bonds

Mr D Eve

Marlborough School Science Department

Quaternary Structure
Quaternary structure is the final step in protein building: it is the structure due to modifications, cofactors (like vitamins and nucleotides), prosthetic groups (like haem, and bound metal ions), glycosylation (the addition of sugar residues through serine or asparagine residues) , and the agglomeration of separate polypeptide chains to form multimeric proteins. Marlborough School
Mr D Eve

Science Department

Haemoglobin

Mr D Eve

Marlborough School Science Department

The Haem Group
One haem group is contained in each of the four subunits of haemoglobin. The Iron atom in the middle is able to bind with oxygen to form oxyhaemoglobin.
Mr D Eve

Marlborough School Science Department

Acknowledgements
• http://www.elmhurst.edu/~chm/vchembook/567tertprotein.html • http://images.google.co.uk/imgres?imgurl=http://kvhs.nbed.nb.ca/ gallant/biology/tertiary_structure.jpg&imgrefurl=http://kvhs.nbed. nb.ca/gallant/biology/biology.html&h=600&w=341&sz=82&tbnid =85_xPGG43P285M:&tbnh=135&tbnw=77&prev=/images%3Fq% 3Dtertiary%2Bstructure%26um%3D1&start=1&sa=X&oi=images &ct=image&cd=1 • http://dl.clackamas.edu/ch106-08/tertiary.htm

Mr D Eve

Marlborough School Science Department