Biology HL

7.5
Proteins

Protein structure

There are four levels to protein structure (or organisation):

! Primary structure
! Secondary structure
! Tertiary structure
! Quaternary structure

Primary structure

The primary level of protein structure is the unique sequence of amino acids held together by
peptide bonds in each polypeptide chain (Fig. 1). There are 20 amino acids and there many
be any number of these and they may be arranged in any order this means that that there is
effectively an infinite number of possible proteins. The order or sequence in which the amino
acids are arranged is determined by the nucleotide base sequence in the DNA of an organism.
Because every organism has its own DNA, every organism has its own unique proteins.

Simply put, the primary structure is a chain of amino acids attached by peptide bonds (CN
bonds), and there may be hundred of amino acids in these polypeptide chains (some repeated).

H O

N Gly Phe Arg C

H OH

Fig. 1: An example of a protein in

its primary structure

The primary structure of a protein determines the next three levels of its organisation. Changing
one amino acid in the chain can completely alter the structure and function of the protein, for
example in sickle cell disease. In this condition, just one amino acid is changed in an otherwise
normal protein of red blood cells (haemoglobin). This is because the R group is changed, so R
group interaction at higher levels of structure is also changed. The result is that red blood cells
are unable to carry oxygen.

Secondary structure

This level of protein structure is created by the formation of hydrogen bonds between the
oxygen from the carboxyl group (COOH, in particular the oxygen in C=O) of one amino acid and
the hydrogen from the amino group (NH2, in particular a single hydrogen atom) of another.

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Proteins

N.B.: !This is not R group interaction secondary structure is made by the formation of
! hydrogen bonds between the carboxyl and amino groups that are present in all
! amino acids, whereas the R group interaction is part of tertiary structure.

The two most common configurations of secondary structure are the -helix and the -pleated
sheet (Fig. 2, Fig. 3 and Fig. 4), and both have regular repeating patterns.

Secondary organisation of polypeptide chains is the reason for

some of the properties of particular proteins. For example, the
hydrogen bonds in -pleated sheets make them strong
structures. Spiders utilise this property of -pleated sheets in the
amino acid responsible for their webs: transthyretin. It contains
O
many pleated sheets joined by hydrogen bonds that contribute
to the strength of the web.

There is a key difference between the -helices and the -

pleated sheets: the hydrogen bonds formed in -helices is an
H intramolecular (within the same molecule) hydrogen bonds,
O whereas the hydrogen bonds formed in -pleated sheets are
often intermolecular (between different molecules) hydrogen
bonds, though not always, as the chain may curve around and
link to itself at a different point.

O H

Fig. 2: An -helix and the Fig. 3: Visual display of -pleat

hydrogen bonds between structure
strands
Usually, intramolecular hydrogen bonds (whether that is in -helices or -pleated sheets) form
globular proteins, whereas intermolecular hydrogen bonding between different polypeptide chains
of amino acids will form a fibrous protein. An example of a protein in its secondary structure is
collagen.

At this point, R groups are not involved they are put on the outward side of -helices.

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Proteins

H N C O

C H H N

O C C H

N H O C

H C N H

C O H C

H C O
N

C H H N

O C C H

N H O C

H C N H

C O H C

Hydrogen bond
Fig. 4: Chemical display of -pleat
structure

Tertiary structure

Tertiary structure is the overall three dimensional structure of the entire polypeptide. The
structure is formed by R group interaction. As there are many different R groups, there are many
ways in which the R groups can interact (or bond).

! ! Ionic bonding between positively and negatively charged sidechains.

! ! Disulphide bonds where covalent bonds are formed between sulphur atoms. They
! ! are often called disulphide bridges owing to their strength.
! ! Hydrogen bonds between polar sidechains.
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Proteins

The interactions cause the polypeptide chain to

bend and fold over itself, resulting in a very
definite three dimensional structure.

Tertiary structure is important in determining the

function of a protein, for example an enzymes
active site (and its specificity). This is the reason
why a change in a single amino acid in the
polypeptide chain can result in a completely
different protein: there may be a change in the
way the R groups interact or they may not interact
at all.

Quaternary Structure
Fig. 5: Visual Sausage model of
tertiary structure Quaternary structure is the three dimensional
structure of proteins that are composed of two or
more polypeptide
chains (called
subunits). Quaternary
structure may also
!
involve the binding of a
prosthetic (non-
polypeptide) group to
form a conjugated
protein.

Several polypeptide
chains interact to form
a single structure and
a functional protein.
These subunits are
held together by weak,
n o n - c o v a l e n t
interactions. Some
Prosthetic group proteins with
Fig. 6: Visual Sausage model of a quaternary structure
conjugated protein in quaternary structure
may include prosthetic or non-polypeptide groups. These proteins are called conjugated
proteins (Fig. 6).

Not all proteins consist of multiple polypeptide chains, so not all proteins have quaternary
structure. Collagen (mentioned earlier) is an example of a secondary structure protein, and has
no quaternary structure.

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Proteins

An example of a conjugated protein is haemoglobin. It is a globular protein that contains 4 haem

groups that contain an iron atom that binds to oxygen. Haemoglobin is also characterised by
the fact that it is made up of four polypeptide chains and it contains two alpha chains and two
beta chains in its polypeptide chains.

Fibrous and globular proteins

Fibrous proteins are composed of many polypeptide chains in a long, narrow shape. They are
usually insoluble in water. One example is collagen, which plays a structural role in the
connective tissue of humans. Actin is another example. It is a major component of human
muscle and interacts with myosin to bring about muscle movement in animals.

Globular proteins are more three-dimensional in their shape and are mostly water soluble.
Haemoglobin, which delivers oxygen to body tissues, is one type of globular protein. The
hormone insulin is another globular protein.

Comparison of fibrous and globular proteins

Fibrous proteins Globular proteins

Repetitive regular sequences of amino acids Irregular amino acid sequences

Actual sequences may very slightly between Sequence highly specific and never varies
two examples of the same protein between two examples of the same protein

Polypeptide chains form long parallel strands Polypeptide chains folded into a spherical
shape

Length of chain may vary in two examples of Length always identical in two examples of
the same protein the same protein

Stable structure Relatively unstable structure

Insoluble Soluble forms colloidal suspensions

Support and structural functions Metabolic functions

Examples include collagen and keratin Examples include all enzymes, some
hormones (e.g. insulin) and haemoglobin

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Proteins
Factors causing protein denaturation
Factor Explanation
Heat Causes the atom of the protein to
vibrate more (i.e. increased
kinetic energy), thus breaking
hydrogen and ionic bonds
Acids Additional H+ ions in acids
combine with COO- groups on
amino acids and form COOH.
Ionic bonds are hence broken
Alkalis Reduced number of H+ ions
causes NH3+ to lose H+ ions and
for NH2. Ionic bonds are hence
broken
Inorganic chemicals The ions of heavy metals such as
mercury and silver are highly
electropositive. They combine
with COO- groups and disrupt
ionic bonds. Similarly, highly
electronegative ions, e.g. cyanide
(CN-) combine with NH3+ groups
and disrupt ionic bonds
Organic chemicals Organic solvents alter hydrogen
bonding within a protein
Mechanical force Physical movement may break
hydrogen bonds
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Example
Coagulation of albumen (boiling
eggs makes the white more
fibrous and less soluble)
The souring of milk by acids (e.g.
Lactobacillus bacterium produces
lactic acids, lowering pH and
causing it to denature the casein,
making in insoluble and thus
forming curds
Many enzymes are inhibited by
being denatured in the presence
of certain ions, e.g. cytochrome
oxidase (respiratory enzyme) in
inhibited by cyanide
Alcohol denatures certain
bacterial proteins. This makes it
useful for sterilisation
On stretching a hair, the hydrogen
bonds in the keratin helix are
broken. The helix is extended and
the hair stretches. If released, the
hair returns to its normal length. If,
however, it is wetted and then
dried under tension, it maintains
its new length the basis of hair
styling.
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Proteins

Polar and non-polar amino acids

Amino acids are often grouped according to the properties of their sidechains (R groups).

Amino acids with non-polar sidechains are hydrophobic. Non-polar amino acids are found in the
regions of proteins that are linked to the hydrophobic area of the cell membrane.

Polar amino acids have hydrophilic properties, and they are found in regions of proteins that are
exposed to water. Membrane proteins include polar amino acids towards the interior and
exterior of the membrane. These amino acids create hydrophilic channels in proteins through
which polar substances can move.

Polar and non-polar amino acids are important in determining the specificity of a enzyme. Each
enzyme has a region called the active site. Only specific substrates can combine with particular
active sites. Combination is possible when fitting occurs. The fitting involves the general
shapes and polar properties of the substrate and of the amino acids exposed at the active site.

Functions of proteins

Function Example

Defence Antibodies (Immunoglobins): group of proteins that act as antibodies to

fight bacteria and viruses

Enzymes Amylase: aids digestion by catalysing the hydrolysis of food groups in

the case of amylase, starch is hydrolysed

Hormones Insulin: a hormone secreted by the pancreas that aids in maintaining the
blood-glucose levels vertebrates

Movement Actin and Myosin: proteins that interact to bring about muscle movement
in animals

Transport Haemoglobin: protein containing iron in its haem groups that transports
oxygen from the lungs to all parts of the body in vertebrates

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