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Physical Structure
Main Concepts

Amino Acids

The building blocks of all proteins are the amino acids. There are about 20 common amino acids, all but one of them have a structure based on a single atom of carbon, to which is attached four different atoms or groups of atoms; a hydrogen atom, an amine group, a carboxylic acid group and a variable group (called here an R-group). It is the varying chemical structure and properties of the R-group that make the amino acids different from one another.

About 9 amino acids have non-polar R-groups and are relatively hydrophobic. Another 6 amino acids have strongly polar R-groups which readily attract water molecules. These are hydrophilic amino acids. The remainder, about 5 amino acids, have R-groups which can ionize. At normal cellular pH's these R-groups become electrically charged, making them even more hydrophilic than the polar amino acids.

Some of the Amino Acids

Amino Acid Abreviation % in hemoglobin # molecules in insulin Year discovered
Alanine Ala 9.0 3 1875
Aspartic Acid Asp 9.6 0 1868
Glutamic Acid Glu 6.6 4 1866
Histidine His 8.8 2 1896
Leucine Leu 14.0 6 1819
Proline Pro 4.8 1 1901
Serine Ser 4.4 3 1865
Tyrosine Tyr 2.9 4 1846

Polypeptides I:
Primary Structure

Polymers of amino acids are called "polypeptides", a name which comes from the type of bond holding the chains of amino acids together. In a joining reaction called a "condensation" or "dehydration synthesis" the nitrogen atom of one amino acid is directly linked to the carbon atom in the acid group of the second amino acid. During this molecular rearrangement, a molecule of water is produced. The resulting group of atoms, which hold the amino acids together, is called a peptide bond.

Any of the 20 different amino acids can occur in any position along a polypeptide chain. This means that there is a very large number of possible chains, even at lengths of only a few amino acids. The number, and sequence, of amino acids in a polypeptide chain is called the primary structure. Every type of polypeptide produced by a cell has a different primary structure. This is a carefully controlled property of the chain and is regulated by the genetic code found in the genes and DNA molecules. All the other properties of polypeptides and proteins stem from the primary structure.

Polypeptides II:
Secondary Structure

In water, polypeptides act and react with themselves and with their environment. The sum of all the forces acting on the complex chains, and their chemical R-groups, bends, twists and forces the polypeptide into fantastic shapes. They coil and fold into complicated three dimensional conformations which are critical to their roles and properties inside cells. The lowest level of three dimensional shape is called the secondary structure. Three types of common secondary structure can be recognized.

Random Walk

is seen in regions of polypeptide where the constituent R-groups act and react to one another. A positively charged R-group could be attracted to a negatively charged R-group forcing the chain to bend until the two R-groups come close together. Alternatively, a second positively charged R-group further down the chain would be repelled by the first positive charge. The chain would stretch out so as to put the largest possible distance between these charges.

Beta Pleated Sheet

is a flexible, strong configuration in which alternate R-groups extend away from the backbone of the chain in opposite directions. This produces a zig-zag effect which is held in place by cross linking hydrogen bonds between adjacent chains. Silk protein, beta-keratin, spider webs, your nails, all contain proteins with high proportions of beta pleated sheet. These proteins resist stretching since their chains are almost fully extended as it is.

Alpha Helix

is a common form of secondary structure seen in many proteins. A series of weak hydrogen bonds form between the atoms of one peptide bond and the atoms of another peptide bond about 3 amino acids further down the chain. These tiny interactions, are, never the less, strong enough to coil the polypeptide into an alpha helix; a structure that looks some what as if the chain of amino acids had been wrapped around a cylinder. These spiral, helical molecules can be stretched. Some proteins, with high helical content, extend easily. Hair and wool readily stretch, but, when the force is released, the helix snaps back into its original conformation, and the protein returns to its original shape.

Tertiary Structure,
becoming a protein

Most proteins fold into complex, three dimensional, globular shapes. Hydrophilic R-groups interact positively with the surrounding water. The entire chain twists until the maximum number of these groups are in full contact with the surrounding water. The interplay between water and the hydrophilic R-groups support the huge protein molecule and help keep it in solution. Conversely, the hydrophobic R-groups become buried deep within the folding macromolecule, far away from the water molecules. These forces, together with other cross-linking effects, hold the giant structure in a three dimensional shape which is distinctive and unique to that protein.

It is at this level of structure that many proteins take on their cellular role or function. As a polypeptide chain, the molecule had no special properties, but as a three dimensional protein, the molecule is capable of performing an astonishing variety of feats. Globular proteins catalyze chemical reactions, others act as defending antibodies within the immune system, and yet others trigger violent bodily reactions as they travel through the blood.

Quaternary Structure

Some globular proteins come together in complexes consisting of two or more subunits. Attached to these subunits can be other, non protein, molecules such as polysaccharides. These higher levels of structure can be seen in a protein molecule such as hemoglobin, a large, four subunit globular protein with four additional non protein additions. This protein carries oxygen around in the blood.


Most of the special properties of proteins stem from their unique three dimensional shapes. When this shape is lost, the protein ceases to function. The process of changing the shape of a protein so that the function is lost is called denaturation.

Proteins are easily denatured by heat. When protein molecules are boiled their properties change. For example, they frequently become insoluble and remain so even when the solution is cooled. Boiling an egg causes the irreversible denaturation of all the proteins it contains, the "white" of the egg, a globular protein, changes shape and hardens into a solid. This denatured protein has the same primary structure as the original protein, but the tertiary structure has been lost; so have all the critical properties of the original or native protein.

Denaturation can be brought about in other ways as well as heat. All proteins can be denatured by extremes of pH; alkaline or acid. They are sensitive to organic solvents and soaps. Beating an egg white will cause mechanical denaturation by increasing the surface area of the liquid. Surface tension then pulls the protein out of shape.

*** Make a Dipeptide ***

© 2003, Professor John Blamire