Protein Structure

©1999 Timothy Paustian, University of Wisconsin-Madison

General Function

Proteins and peptides (small proteins) are essential to the cell. They serve two major functions in the cell. Some proteins are enzymes that catalyze most biological reactions in a living organism. Other proteins perform a structural role for the cell - either in the cell wall, the cell membrane or in the cytoplasm. In this section, we will look at the basic structure that all proteins have in common.

Primary Stucture

Protiens are polymers of amino acids. Amino acids are primary amines that contain an alpha carbon that is connected to an amino (NH³) group, a carboxyl group (COOH), and a variable side group (R) - Figure 1. The side group gives each amino acid its distinctive properties and helps to dictate the folding of the protein.

Figure 1. A general amino acid.

Polymers of amino acids are created by linking an amino group to a caroboxyl group on another amino acid. This is termed a peptide bond - Figure 2.

Figure 2. A peptide bond

There are 20 common amino acids found in proteins and these amino acids can be classified into 3 groups; polar, non-polar and charged. Figure 3 shows the chemical structure of the amino acids.

Figure 3. The common amino acids

Peptides and proteins are formed when a ribosome and the rest of the translation machinery link 10 - 10,000 amino acids together in a long polymer. This long chain is termed the primary sequence. The properties of the protein are determined, for the most part, by this primary sequence. In many cases an alteration of any amino acid in the sequence will result in a loss of function for the protein (a mutation). Genetic diseases in humans are often caused by changes in important proteins that causes illness. Sickle cell anemia is caused by a single amino acid change from glutamic acid to valine at position 6 of the hemoglobin protein, see Figure 4. Below is the primary sequence of hemoglobin, the oxygen carrying protein found in humans and other mammals.

Figure 4. Hemoglobin amino acid sequence. Only the first 26 amino acids are shown.

Secondary Structure

Basic attractive forces

During and after synthesis the primary sequence will associate in a fashion that leads to the most stable, "comfortable" structure for the protein. How a protein folds is largely dictated by the primary sequence of amino acids. Each amino acid in the sequence will associate with other amino acids to conserve the most energy. This structure is stabilized by hydrogen bonds, hydrophobic interactions, ionic interactions, and sulfhydryl linkages.

Hydrogen bonds are sharing of electrons between electron starved hydrogen atoms and electron rich (typically oxygen and nitrogen) neighboring atoms. The hydrongen atoms are attracted to the extra electrons and tend to stay in the vicinity of the oxygen or nitrogen. This is not a covalent bond, but large numbers of them can add significantly to the stability of a protein.

Hydrophobic interactions (water hating) consist of the attraction of non-polar amino acids to one another. The hydrophobic amino acids can be thought of as oil in water. When you place some oil in a bottle of water, the oil has a tendency to separate from the water and form one large bleb (that is a scientific term). If you shake the bottle, the oil is dispersed, but in a little while it all congregates again. This is hydrophobic interactions at work. The same process is functioning at the molecular level. Hydrophobic amino acids try to hide themselves away from the water on the outside of the protein by all congregating on the inside of the protein. This grouping together helps define the structure of a protein.

Ionic interactions are the attraction of opposite charges for one another. Negatively charged amino acid side groups, such as glutamate and aspartate are attracted to positively charged amino acid side groups such as lysine, arginine, and histidine.

Finally there are sulfhydryl linkages. These are covalent bonds between cysteine groups. Cysteine is a unique amino acid in that it has a sulfur group available for binding to other groups. Often in proteins, adjacent sulfhydryl groups on cysteines will form a covalent link to help stabilize a protein - Figure 5.

Figure 5. Two views of sulfhydryl linkages

The chemical structure of a sulhydryl bond	A sulfhydryl bond in a peptide

Common Secondary Structures

Proteins will often have stretches of amino acids that will associate into two common structures. These are the alpha helix and the beta (pleated) sheet. Formation of these structures is driven by favorable hydrogen bonding and hydrophobic interactions between nearby amino acids in the protein.

The alpha helix resembles a ribbon of amino acids wrapped around a tube to form a stair case like structure. Below is pictured a ribbon and ball and stick diagram of a model alpha helix. This structure is very stable, yet flexible and is often seen in parts of a protein that may need to bend or move.

Figure 6. The alpha helix

Ribbon

Ball and stick

In the beta sheet, two planes of amino acids will form, lining up in such a fashion so that hydrogen bonds can form between facing amino acids in each sheet. The beta pleated sheet or beta sheet is different than the alpha helix in that far distant amino acids in the protein can come togeher to form this structure. Also, the structure tends to be rigid and less flexible.

Figure 7. The beta sheet

Ribbon top view	Ribbon side view
Ball and stick side view

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