Proteins

Proteins are an extremely important class of macromolecule in living organisms. More than 50% of
the dry mass of most cells is protein. Proteins have many important functions. For example:

• all enzymes are proteins

• proteins are essential components of cell membrane their functions in membranes, such as
receptor proteins and signalling proteins.
• some hormones are proteins – for example, insulin and glucagon
• the oxygen-carrying pigments haemoglobin and myoglobin are proteins
• antibodies, which attack and destroy invading microorganisms, are proteins
• collagen, another protein, adds strength to many animal tissues, such as bone and the walls
of arteries
• hair, nails and the surface layers of skin contain the protein keratin
• actin and myosin are the proteins responsible for muscle contraction
• proteins may be storage products – for example, casein milk and ovalbumin in egg white.

The diversity of the amino acid content and sequence is the source of diversity in proteins. Peptide
bonds are the linkages between amino acids. Proteins are polymers of amino acids arranged in linear
sequence. An amino acid contains an amino group (–NH2) and a carboxylic group (-COOH) bonded to
a central carbon atom. A hydrogen atom and a side group designated R are bonded to the same
carbon atom. R simply means the rest of the molecule. The basic structure of each of the 20 amino
acids commonly found in proteins is the same but the R side group is different.

Both the amino (– NH2) and carboxyl (–COOH) regions on an amino acid ionise in solution forming
–NH3+ and –COO-. Ionisation occurs according to the pH. For each amino acid, there is a pH at which
the overall charge of the molecule is zero. In addition to the 20 amino acids used by living systems to
build proteins, there are others not used in building proteins but with various other functions.

Protein molecules are large and complex molecules containing several hundred amino acid units.
The possible number of different amino acid sequences and therefore the possible variety of protein
molecules is enormous. Amino acids may be polar, non-polar or charged and this influences the
hydrophobic or hydrophilic nature of the proteins that they make up.
 Amino acids are joined together in a condensation reaction where the amino group is linked to the
carboxylic group of a second amino acid and a molecule of water is lost. The covalent bond formed is
called a peptide bond. A molecule that results from linking many amino acids together is called a
polypeptide. The beginning of the polypeptide chain is the amino group of the first amino acid and is
called the N-terminus. The end of the polypeptide chain is the carboxyl group of the last amino acid
or the C-terminus.

The primary, secondary and quaternary structure of proteins

The Primary Structure of Proteins- Polypeptides
Through a series of condensation reactions, many amino acid monomers can be joined
together in a process called polymerisation. The resulting chain of many hundreds of amino
acids is called a polypeptide. The sequence of amino acids in a polypeptide chain forms the
primary structure of any protein. There are an enormous number of different possible
primary structures. Even a change in one amino acid in a chain made up of thousands may
completely alter the properties of the polypeptide or protein.
Secondary structure
The two main types of protein secondary structure are the -helix and the -pleated sheet.
The -helix is held in shape by hydrogen bonds. Hydrogen bonds are formed between the
double-bonded oxygen atom in one amino acid and the hydrogen atom of the amino group
in another amino acid situated four amino acids along the chain. The R groups extend
outward from the -helix. Proteins may have one portion of their secondary structure as an
α-helix and another portion as a β-pleated sheet.
Hair is made up of insoluble fibrous proteins called keratins. Individual molecules of keratin
form an α-helix that is held together by hydrogen bonds. Each molecule of keratin is then
cross-linked to other keratin molecules by disulfide bridges between the cysteine residues.
The amino acid cysteine contains sulfur and a disulfide bridge forms when two cysteines
form covalent bonds between themselves. Hair can be stretched because stretching
requires that only the hydrogen bonds of the α-helix be broken and this allows the helix to
be extended; when the tension on the hair is released, the hydrogen bonds and the -helix
are re-established. The covalent bonds (disulfide bridges) in the hair are not broken in
simple stretching. The use of a chemical perm or hair straightener does break some of the
covalent bonds between neighbouring keratin molecules.
In the β-pleated sheet, polypeptide chains are lined up in parallel and are linked to one
another by hydrogen bonds; this results in a zigzag shape. The chains are joined together
by hydrogen bonds formed between the C=0 and N–H of one polypeptide chain and the C=0
and N–H on the adjacent chains. In some proteins, two or more polypeptide chains are
aligned to form the β-pleated sheet. In other proteins, the polypeptide chain loops back and
forth in such a way that adjacent portions of the same chain hydrogen bond and form the
β-pleated sheet. Proteins with an α-helix or β-pleated sheet secondary structure are called
fibrous proteins. Fibrous proteins have a variety of important structural roles providing
support and shape to organisms. Silk is a fibrous protein composed of only β-pleated sheets.

α-helix

β-pleated

Tertiary Structure
The α-helices or β-pleated sheets of the secondary protein structures can be twisted and
folded even more to give the complex, and often unique, 3-D structure of each protein. This
is known as the tertiary structure and is the result of four possible types of bonds that can
arise between each amino acid. These are:

• Hydrogen bonds can form between a wide variety of R groups. Results from the
attraction between the electronegative oxygen atoms on the -CO- groups and the
electropositive H atoms on either -OH or -NH groups.
• Disulfide bonds (bridges) found between sulfur atoms in the molecules of the amino
acid cysteine. They are covalent bonds and as such form very strong links which
make the tertiary structure very stable.
• Ionic bonds form between R groups containing amine and carboxyl groups that are
not involve in peptide bonds. These bonds are weaker than disulfide bridges and can
be easily broken by changes in pH.
• Hydrophobic interactions occur between R groups which are non-polar or
hydrophobic. As a result, they may fold or twist the peptide chain as they take up a
position towards the centre of the protein, further away from the watery medium
outside.
Proteins with a 3D structure fall into two main types:
Globular - These tend to form ball-like structures where hydrophobic parts are
towards the centre and hydrophilic are towards the edges, which makes them water
soluble. They usually have metabolic roles, for example: enzymes in all organisms,
plasma proteins and antibodies in mammals.
 Fibrous - They proteins form long fibres and mostly consist of repeated sequences of
amino acids which are insoluble in water. They usually have structural roles, such as:
Collagen in bone and cartilage, Keratin in fingernails and hair.

Quaternary Structure
Some proteins are made up of multiple polypeptide chains, sometimes with an inorganic
component (for example, a haem group in haemoglobin) called a Prosthetic Group. These
proteins will only be able to function if all subunits are present.
Quaternary Structure: The structure formed when two or more polypeptide chains join
together, sometimes with an inorganic component, to form a protein.
Haemoglobin and Collagen
Haemoglobin is a water soluble globular protein which is composed of two α polypeptide
chains, two β polypeptide chains and an inorganic prosthetic haem group. Its function is to
carry oxygen around in the blood, and it is facilitated in doing so by the presence of the
haem group which contains a Fe2+ ion, onto which the oxygen molecules can bind.
Collagen is a fibrous protein consisting of three polypeptide chains wound around each
other. Each of the three chains is a coil itself. Hydrogen bonds form between these coils,
which are around 1000 amino acids in length, which gives the structure strength. This is
important given collagen’s role, as structural protein. This strength is increased by the fact
that collagen molecules form further chains with other collagen molecules and form
Covalent Cross Links with each other, which are staggered along the molecules to further
increase stability. Collagen molecules wrapped around each other form Collagen Fibrils
which themselves form Collagen Fibres.
 Collagen has many functions:
• Form the structure of bones
• Makes up cartilage and connective tissue
• Prevents blood that is being pumped at high pressure from bursting the walls of
arteries
• Is the main component of tendons, which connect skeletal muscles to bones

 Haemoglobin may be compared with Collagen as such:

• Basic Shape - Haemoglobin is globular while Collagen is fibrous
• Solubility - Haemoglobin is soluble in water while Collagen is insoluble
• Amino Acid Constituents - Haemoglobin contains a wide range of amino acids
while Collagen has 35% of it primary structure made up of Glycine
• Prosthetic Group - Haemoglobin contains a haem prosthetic group while
Collagen doesn’t possess a prosthetic group
• Tertiary Structure - Much of the Haemoglobin molecule is wound into α helices
while much of the Collagen molecule is made up of left handed helix structures
Features Haemoglobin Collagen

Shape Globular Fibrous

Solubiliy Soluble in water Insoluble in water

Prosthetic Group Haem None

Tertiary Structure Mostly alpha helices Left handed helices