We have already mentioned proteins, since there is almost no biological process that does not rely on them.

Proteins derive their name from the ancient, but minor, Greek sea-god Proteus who, like your typical sea-god, could change shape. The name acknowledges the many different functions and properties of proteins.

Proteins can act as catalysts and regulators of chemical reactions. They control the expression of genes, how genes respond to internal and external signals, and the replication of the genetic material.

They can be structural components, determining both the shape and mechanical properties of cells and tissues.

They can be motors, responsible for movements within cells, the movement of cells, tissues and the organism as a whole.

Proteins are composed of -amino acids linked together by peptide bonds into polypeptide chains.

An amino acid is characterized by an amino group (-NH₂) and a carboxylic acid group (-COOH) linked to a carbon, known as the -carbon.

Also attached to the -carbon is a H and various 'R-groups' or 'side-chains'.

The four groups attached to the -carbon are arranged at the vertices of a tetrahedron.

If the four groups are different from one another, as they are in all amino acids except glycine, there are two possible stereoisomers, which are known as enantiomers.

These enantiomers are mirror images of one another and are termed the L- and D- forms.

Only L-type amino acids are found in proteins, even though there is no theoretical reason that proteins cannot be made of both types of amino acids.

Even though there are hundreds of different amino acids known, only 19 amino acids and one imino acid, proline, are found in proteins.

These amino acids differ in their R-groups.

Some of these R-groups are highly hydrophobic, some are hydrophilic, some are positively or negatively charged.

The different R-groups provide proteins with a range of chemical properties.

Building a polypeptide

Polymers are chains of subunits, monomers, linked together by chemical bonds.

The bond between two amino acids is known as a peptide bond. Two amino acids, joined together by a peptide bond, are known as a dipeptide.

An amino acid polymer is known as a polypeptide. This is a complex polymer, composed of 20 different possible monomers that can, in theory, be linked together in any imaginable order.

The formation of a peptide bond involves a condensation / dehydration reaction. Two molecules become one and water is released.

This generates an unbranched, linear polymer.

The peptide bond has a number of characteristics that are critical in determining how polypeptides behave. Although drawn as a single bond, the peptide bond behaves more like double bond.

While there is free rotation around a single bond rotation, around a peptide bond is constrained.

Moreover, the carbonyl oxygen (-C=O) acts as a H-bond acceptor, while the amino hydrogen (-N-H) acts as a H-bond donor.

Proline is not an amino acid, but rather an imino acid.

It makes a rather different type of peptide bond which is not nearly as constrained as a typical peptide bond.

Proline peptide bonds are found in the cis configuration ~100 times as often as those between other amino acids.

There is no H-bond donor in the proline peptide bond and the presence of proline leads to a bend or kink in the polypeptide chain.

Water, polypeptide synthesis and folding

Were it not for the various R-groups polypeptides would assume an extended configuration in water. An example is polyglycine.

H-bond donors and acceptor groups in polypeptide backbone would form H-bonds with each other and with water molecules.

More typical polypeptides have all of the different R-groups in various proportions. Many of these R-groups are highly hydrophobic. Their presence makes an extended configuration energetically unfavorable.

Very much like the process by which lipids self-assemble to form micelles and bilayers, a polypeptide in aqueous solution will collapse onto itself in order to remove as many of these hydrophobic residues from contact with water as possible.

It is a basic assumption of structural biology that the final folded state of a polypeptide is determined by the sequence of amino acids along its length, and that this final structure is the state of lowest energy

This sequence of amino acids is known as the primary structure of the polypeptide.

We write the amino acid sequence of a polypeptide from its N- or amino terminus to its C- or carboxyl terminus, with the N-terminus to the left and the C-terminus to the right.

Proteins structure is commonly presented in a hierarchical manner.

While this is an over-simplification, it is a good place to start.

We will consider the actual process of protein synthesis, known as translation, in the next reading.

As it is being synthesized, the polypeptide chain begins to fold.

The path to the native state is not necessarily a smooth or unambiguous one.

The folding polypeptide can get 'stuck' in a local energy minimum.

If a polypeptide get stuck, there are mechanisms to unfold it and let it 'try' again to reach its native state.

Secondary structure features

All polypeptides share a common backbone structure made up of peptide bonds.It is therefore not surprising that there are common patterns or motifs in polypeptide folding.

The first of these, the helix, was discovered by Linus Pauling and Robert Corey, and reported in 1951.

Linus at age 5.

This was followed shortly thereafter by the structure of the ß-sheet.

The forces that drive the formation of the helix and the ß-sheet will be familiar. They are they same forces that underlie water structure.

In an -helix all of the possible H-bonds involving the peptide bond donor and acceptor groups are formed. This stabilizes the structure.

In an -helix, the R-groups point outward from the long axis of the helix.

In ß-sheets, the H-bonds between the peptide bond donor and acceptor groups are made between either parallel or anti-parallel polypeptide chains.

These are anti-parallel ß-sheets

The R-groups point out of and into the plane of the sheet.

The pattern of -helices, ß-sheets and connecting regions is known as the secondary structure of the polypeptide.

The key factor that determines the specific details of polypeptide folding is the interaction between R-groups, not only with one another but with water and dissolved ions.

In a water soluble polypeptide, most but not necessarily all of the surface R-groups will by hydrophilic.

Hydrophobic groups will tend to be buried in the polypeptide's interior.

Some polypeptides are inserted into membranes. In these polypeptides, hydrophobic R-groups on the surface of the folded polypeptide will interact with the hydrophobic interior of the lipid bilayer

A protein is a functional entity. In many cases a protein is composed of multiple polypeptides.

A protein that contains multiple polypeptides, whether of the same or different types, is said to have a quaternary structure.

A protein with two polypeptide subunits.

There are also higher levels of polypeptide organization. For example, a specific polypeptide may be a component for a number of different proteins.

The polypeptide may form stable interactions and be an integral part of a single protein molecule for its entire existence,

Alternatively, the polypeptide may actively exchange partners and be part of a number of a different proteins during its lifetime.

A polypeptide that takes part in many dynamic interactions is part of a regulatory network. Such a polypeptide can be said to have a quinary structure.

Other factors in protein structure

In addition to polypeptides, proteins can include non-amino acid-based components, known generically as co-factors.

A protein minus its cofactors is known as the apoprotein or apoenzyme,

Together with its cofactors, it is known as the holoprotein or holoenzyme.

A protein without its cofactors is inactive and often unstable.

Cofactors can range in complexity from a single metal atom to quite complex molecules, such as the vitamin B₁₂

Another important stabilizing element in protein structure is the formation of disulfide bonds between cysteine residues.

These are strong covalent bonds. They are generally formed once the polypeptide has folded correctly and stabilize the final folded structure.

If they form too early, however, they can block the correct folding of the polypeptide and must be removed for correct folding to occur.