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Protein Structure

Primary Structure

Proteins are made up of polypeptide chains, which are amino acids joined together with peptide bonds. The
unique sequence of amino acids that make up a protein or polypeptide chain is called the Primary Structure.

Primary Structure: The unique sequence of amino acids that makes up a protein or polypeptide chain.

Peptide bonds are created by enzyme catalysed condensation reactions and broken down by enzyme
catalysed hydrolysis reactions. Breaking down proteins is important in many areas of the body, not merely in
digestion. For example, in hormone regulation, cells that are targeted by hormones contain enzymes to break
down those hormones. This stops their effects from being permanent and allows them to be controlled.

Secondary Structure

After synthesis, polypeptide chains are folded or pleated into different shapes, called their Secondary
Structure. Two common examples of secondary structures are Alpha Helices and Beta Pleated Sheets.
Secondary structure is held together by many Hydrogen bonds, overall giving the shape great stability.

Secondary Structure: The way in which the primary structure of a polypeptide chain folds.

Tertiary Structure

The final 3D structure of a protein is its Tertiary Structure, which pertains to the shaping of the secondary
structure. This may involve coiling or pleating, often with straight chains of amino acids in between.

Tertiary Structure: The final 3D structure of a protein, entailing the shaping of a secondary structure.

Tertiary structure is held together by four different bonds and interactions:


Disulphide Bonds - Where two Cysteine amino acids are found together, a strong double
bond (S=S) is formed between the Sulphur atoms within the Cysteine monomers.

Ionic Bonds - If two oppositely charged 'R' groups (+ve and -ve) are found close to each other,
and ionic bond forms between them.


Hydrogen Bonds - Your typical everyday Hydrogen bonds.

Hydrophobic and Hydrophilic Interactions - Some amino acids may be hydrophobic while
others are hydrophilic. In a water based environment, a globular protein will orientate itself such that it's
hydrophobic parts are towards its centre and its hydrophilic parts are towards its edges
Tertiary structure can be broken by the action of heat. Increasing the kinetic energy of protein with a tertiary
structure makes it vibrate more, and so the bonds that maintain its shape (which are mainly weak, non-covalent
bonds) will be more likely to break. When a protein loses its shape in this way it is said to be Denatured. Even
when cool the protein will not (or is highly unlikely to) form its original complex shape.
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 haemoglogin) 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 polypeptide chains, two
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 helices while much of
the Collagen molecule is made up of left handed helix structures

The Structure of Proteins

Proteins are polymers of amino acids covalently linked through peptide bonds into a
chain. Within and outside of cells, proteins serve a myriad of functions, including
structural roles (cytoskeleton), as catalysts (enzymes), transporter to ferry ions and
molecules across membranes, and hormones to name just a few.
With few exceptions, biotechnology is about understanding, modifying and
ultimately exploiting proteins for new and useful purposes. To accomplish these
goals, one would like to have a firm grasp of protein structure and how structure relates
to function. This goal is, of course, much easier to articulate than to realize! The
objective of this brief review is to summarize only the fundamental concepts of protein
Amino Acids

Proteins are polymers of amino acids joined together by peptide bonds. There are 20
different amino acids that make up essentially all proteins on earth. Each of these amino
acids has a fundamental design composed of a central carbon (also called the alpha
carbon) bonded to:

a hydrogen

a carboxyl group

an amino group

a unique side chain or R-group

Thus, the characteristic that distinguishes one amino acid from another is its unique
side chain, and it is the side chain that dictates an amino acids chemical
properties. Examples of three amino acids are shown below, and structures of all 20 are
available. Note that the amino acids are shown with the amino and carboxyl groups
ionized, as they are at physiologic pH.

Except for glycine, which has a hydrogen as its R-group, there is asymmetry about the
alpha carbon in all amino acids. Because of this, all amino acids except glycine can exist
in either of two mirror-image forms. The two forms - called stereoisomers - are referred
to as D and L amino acids. With rare exceptions, all of the amino acids in proteins are L
amino acids.
The unique side chains confer unique chemical properties on amino acids, and
dictate how each amino acid interacts with the others in a protein. Amino acids can
thus be classified as being hydrophobic versus hydrophilic, and uncharged versus
positively-charged versus negatively-charged. Ultimately, the three dimensional
conformation of a protein - and its activity - is determined by complex interactions
among side chains. Some aspects of protein structure can be deduced by examining the
properties of clusters of amino acids. For example, a computer program that plots the
hydrophobicity profile is often used to predict membrane-spanning regions of a protein
or regions that are likely to be immunogenic.
Peptides and Proteins

Amino acids are covalently bonded together in chains by peptide bonds. If the chain
length is short (say less than 30 amino acids) it is called a peptide; longer chains are
called polypeptides or proteins. Peptide bonds are formed between the carboxyl
group of one amino acid and the amino group of the next amino acid. Peptide bond
formation occurs in a condensation reaction involving loss of a molecule of water.

The head-to-tail arrangment of amino acids in a protein means that there is a amino
group on one end (called the amino-terminus or N-terminus) and a carboxyl group on the
other end (carboxyl-terminus or C-terminus). The carboxy-terminal amino acid
corresponds to the last one added to the chain during translation of the messenger

Levels of Protein Structure

Structural features of proteins are usually described at four levels of complexity:

Primary structure: the linear arrangment of amino acids in a protein

and the location of covalent linkages such as disulfide bonds between
amino acids.

Secondary structure: areas of folding or coiling within a protein;

examples include alpha helices and pleated sheets, which are
stabilized by hydrogen bonding.

Tertiary structure: the final three-dimensional structure of a protein,

which results from a large number of non-covalent interactions
between amino acids.

Quaternary structure: non-covalent interactions that bind multiple

polypeptides into a single, larger protein. Hemoglobin has quaternary
structure due to association of two alpha globin and two beta globin

The primary structure of a protein can readily be deduced from the nucleotide sequence
of the corresponding messenger RNA. Based on primary structure, many features of
secondary structure can be predicted with the aid of computer programs. However,
predicting protein tertiary structure remains a very tough problem, although some

Examples of Proteins with Primary Structures

Last Updated: Nov 09, 2015 | By Sylvie Tremblay, MSc

A smattering of blood cells. Photo Credit Usere6035d91_515/iStock/Getty Images

Your body contains thousands of genes, which code for thousands of different proteins. Each protein, which is made up of a sequence of
amino acids, contributes to the structure or function of your cells by supporting your metabolism, promoting cellular communication, and
supporting the shape and structure of your cells. Each of your proteins has a primary structure, which is important for how the protein

Protein Structure
Protein structure is classified on four levels: primary, secondary, tertiary and quarternary. The primary structure of proteins refers to the sequence of amino
acids that make up a protein chain, or polypeptide. Each protein has a unique primary structure that differs in both the order of amino acids in the
polypeptide and the total number of amino acids that make up the protein molecule. The secondary and tertiary structures refer to the way the polypeptide
is twisted and bent into a three-dimensional shape to make a functional protein. Quaternary structure refers to the way two or more polypeptides interact to
make up a functional protein. Every protein in your body has a primary, secondary and tertiary structure, but only some proteins have a quaternary

One example of a protein with a primary structure is hemoglobin. This protein, found on your red blood cells, helps provide the tissues
throughout your body with a constant supply of oxygen. The primary structure of hemoglobin is important because a change in only one
amino acid can disrupt hemoglobin's function. For example, a single amino acid change to hemoglobin's primary structure can cause sickle
cell anemia, a blood condition characterized by dysfunctional, sickle-shaped red blood cells.

Another protein with important primary structure is hexosaminidase, a protein that contributes to the function of cellular compartments called lysozymes.
Maintaining lysozyme function is important to your health, since these compartments help your cells dispose of molecules that might otherwise harm the

cell. A mutation in the primary structure of hexosaminidase can disrupt lysozyme function in the brain, leading to fatal Tay-Sachs disease. As a result,
babies often undergo genetic testing for hexosaminidase mutations, to aid in early diagnosis of the disease.

Dystrophin is another protein with a primary structure. The presence of dystrophin contributes to muscle functioning, and the protein helps maintain the
structure of your muscle fibers. Genetic mutations that change the primary structure of dystrophin -- such as the substitution of one amino acid for another,
or deletions of amino acids -- can harm your muscle fibers, leading to diseases such as Duchenne muscular dystrophy.

The tertiary structure for myoglobin is
fairly well understood and is shown here.
Myoglobin has an alpha helix which then
can be viewed as being enclosed in this
blue sheath, the sheath doesn't exist but
we can draw it that way. That helix folds
back upon itself into what's referred to as
the tertiary structure of myoglobin. Bonds
between the side groups of the amino acid
residues are responsible for holding
together the tertiary structure of this

Bond Types Stabilizing Tertiary Structure

The kinds of bonds that can exist between the side groups include:
Van der Waals bonds if the side groups are nonpolar.
Hydrogen bonds if the side groups contain hydroxyl or amino groups.
Ionic bonds if the side groups are acids and bases that can transfer protons from one to
another making a carboxylate ion, which is negative, and essentially an ammonium or
quaternary ammonium ion which is positive.
Covalent bonds if the side groups are cysteine residues in which the sulfur atoms are
bonded together by the removal of two hydrogen atoms.

In summary, the tertiary structure of a protein is held together by the bonds

formed by the side groups, and there is quite a variety of different bonds
that can cause the tertiary structure to form.

Primary Structure

Of course, the formation or the putting

together of a protein does not stop at
the dipeptide stage. Instead, these two
amino acid residues are bonded to
another amino acid, which in turn is
bonded to another, which in turn is
bonded to still more. In the process,
quite an extensive arrangement of
amino acid residues are built up to
form a protein. This sequence of amino
acid residues is generally represented
using the abbreviations and is referred
to as the primary structure of the

The primary structure or amino acid sequence is unique for each protein.
The sequence in which the amino acids are attached to one another
ultimately is dependent on the genetic code from DNA. This primary
structure dictates the function of the protein indirectly through additional
levels of structure.
Consider this analogy, the nature of a garden is dictated by the plants that
are in it. It's function, whether it is to provide shade, protection, privacy,
food or tranquility, is going to be dictated by the individual plants selected
and the sequence and orientation of them with respect to one another.
Similarly, what a protein will be able to do is going to be determined by
what amino acids are joined to one another and the sequence in which they
are joined. However, the primary structure alone cannot carry out the
functions of protein. The amino acids bonded to one another in a line don't
make a protein function anymore than plants lined up along a roadside or in
a nursery make a garden.

Secondary Structure

Once the primary structure has been created, a secondary structure of some sort
Alpha Helix

Here we have representation of

a primary structure. It consists of a
sequence of amino acid residues. In
this case I have left out the hydrogen
and the side group from the alpha
carbon. I just want to ignore those for
a moment.

One of the most common types of

secondary structure is referred to as
an alpha helix. Essentially what is
involved in an alpha helix is that the
primary structure of the protein twists
around upon itself in such a way,
somewhat like rolling up this paper
model, to form a recurring pattern
that is very important.

The hydrogen from the amino group

lines up with the oxygen from a
carbonyl group. That happens over
and over again in this structure. So
you can see that hydrogen
bonding can occur with this
arrangement of amino acids in an
alpha helix.

If we were to build a model of this

alpha helix and consider bond angles,
you would find that it doesn't work
out quite as smoothly as what is
shown here.
Also, if you consider the side
chains that I originally chose to
ignore, you would see that they tend

to stick out on the outsides of the


The type and location of these side

groups is very important in
determining the ultimate
structure and also the function of a
particular protein.

Beta Sheet
It is also possible for the protein's
strands to line up side by side with
one another and form hydrogen bonds
in this way. When that happens with
the strands both running in the same
direction it is called parallel.

When that happens with the strands

running in the opposite direction it's

Parallel or antiparallel, this particular kind of secondary structure is referred to

as beta sheet structure. These strands, of course, are not completely flat as
shown on this screen. The amide bond portion is flat but the molecules bend on
both sides of the alpha-carbon with tetrahedral angles. Consequently they fold up
and down and these structures are quite often called beta pleated sheets.
Collagen Helix

A third type of secondary structure

involves three strands of protein
bonded together between the chains
with hydrogen bonds and then twisted
into a helix that is referred to as
a collagen helix. That occurs
primarily (perhaps exclusively) in
protein known as collagen.

Secondary Structure Mixes

Proteins generally have a mix of different kinds of secondary structure. They are
rarely, to my knowledge, all of a particular type. One part of a particular protein
may have an alpha helix, whereas another part can be folded back in the beta
sheet arrangement.
Whatever type of secondary structure is involved in a particular protein, the
secondary structure is held in place by hydrogen bonding interactions between
the amino group of the amino acid residue and the carbonyl group of another
amino acid residue.
Secondary strutureRESULTS in the side groups of the amino acid chain of the
protein chain sticking out to the side. Certain kinds of side groups will enhance
the formation of alpha helix, others will enhance the formation of beta sheet and
so on. But whatever the secondary structure happens to be, the side groups are
going to be sticking out.

Quaternary Structure

Some proteins such as the hemoglobin

represented here, have more than one
string of amino acids which are then
hooked together in what is called
the quaternary structure. Proteins
that contain more than one chain of
amino acids are called oligomeric
proteins and each chain is called a

These chains are held together to form the larger protein by bonds that
exist between the side groups of different chains. As with tertiary structure,
the bonds involved in holding these separate chains together can be van der
Waals bonds, hydrogen bonds, ionic bonds, or at times covalent bonds.