Proteins

Generalized structure of an amino acid

Proteins are composed of long chains of recurring monomers called amino acids
● Each amino acid contains a central alpha carbon linked to an amine group,
carboxyl group, a variable group and a hydrogen atom

There are 20 different amino acids which are universal to all living organisms
● Each type of amino acid differs in the composition of their variable side chain
(denoted ‘R’)

Amino acids can be covalently joined together via condensation reactions to form a
dipeptide and water
● The bond that is created is called a peptide bond and forms between the amine
and carboxyl groups of adjacent amino acids

Long chains of covalently bonded amino acids are called polypeptides and these chains
can be broken down via hydrolysis reactions (requires water to reverse the process)

Polypeptide chains are composed of 20 different types of amino acids, each with specific
variable side chain
● These side chains will have distinct chemical properties (e.g. charged, non-polar,
etc.) and hence cause the protein to fold differently according to its specific
position within the polypeptide chain
● The way a protein molecule folds plays a critical role in determining its eventual
function and level of biological activity
As most natural polypeptide chains contain between 50 – 2000 amino acid residues,
organisms are capable of producing a huge range of possible polypeptides
● Consequently, proteins are a very diverse class of compounds and may serve a
number of different roles within a cell

Functions of Proteins
Proteins perform an array of functions:
● Structure (collagen, spider silk)
● Hormones (insulin, glucagon)
● Immunity (antibodies)
● Transport (protein channels)
● Sensations (rhodopsin)
● Movement (actin, myosin)
● Enzymes (Rubisco, amylase)

Denaturation

Denaturation is a structural change in a protein that results in the loss (usually

permanent) of its biological properties
● Because the way a protein folds determines its function, any change or
abrogation of the three dimensional structure will alter its activity

Denaturation of proteins can usually be caused by two key conditions – heat (high
temperatures) and pH

Temperature:
● High levels of thermal energy may disrupt the hydrogen bonds that hold the
protein together
● As these bonds are broken, the protein will begin to unfold and lose its capacity to
function as intended
● Temperatures at which proteins denature may vary, but most human proteins
function optimally at body temperature (~37ºC)

pH:
● Amino acids are zwitterions, neutral molecules possessing both negatively (COO–)
and positively (NH3+) charged regions
● Changing the pH will alter the charge of the protein, which in turn will alter protein
solubility and overall shape
● All proteins have an optimal pH which is dependent on the environment in which
it functions (e.g. stomach proteins require an acidic environment to operate,
whereas blood proteins function best at a neutral pH)
 Function Example Description

Structure Collagen Used in skin to prevent tearing, in bones to prevent

fractures, and ligaments to give tensile strength

Spider silk Used to make webs for catching prey and lifelines on which
spiders suspend themselves. It has very high tensile
strength and becomes stronger when stretched

Hormones Insulin Is carried dissolved in blood and binds specifically and

reversibly to insulin receptors in the membranes of body
cells, causing the cells to absorb glucose and lower glucose
concentration

Immunity Immunoglobulins Antibodies that bind to antigens on pathogens

Transport Hemoglobin A protein found in red blood cells that is responsible for the
transport of oxygen

Cytochrome A group of proteins located in the mitochondria involved in

electron transport chain

Sensation Rhodopsin A pigment in the photoreceptor cells of the retina that is

responsible for the detection of light

Enzymes Rubisco An enzyme involved in the light independent stage of

photosynthesis

Chemical diversity in proteins

● The R-group determines the folding pattern and functionality of the protein
● Different R-groups will form bonds with each other, causing the protein to fold
into different shapes

The structure of protein has 4 levels of complexity, primary, secondary, tertiary and
quaternary.

The primary structure

● Is the linear sequence of amino acids in a polypeptide

● The backbone is a repeating sequence of atoms linked by covalent bonds.
● The bond angles are all tetrahedral and there can be rotation about the bonds
between the alpha carbon atoms and adjacent nitrogen and carbon atoms
● This allows polypeptides to fold into almost any three-dimensional shape
The secondary structure

● At regular intervals along the poly-peptide chain there are c=o and N=H groups
● Since all of them are polar, and there being a slight difference in charge between
H and O, hydrogen bonds form between these groups
● Even though hydrogen bonds are individually weak, due to the frequency of
recurrence they are strong enough to stablise distinctive conformational
structures
● 2 common types of structures are
● The ɑ- helix
○ The polypeptide is wound into a helical shape, with hydrogen bonds
between adjacent turns of the helix
● The 𝛃 - pleated sheet
○ 2 or more sections of the polypeptide are arranged in parallel with
hydrogen bonds between them
○ The sections of polypeptide run in opposite directions, forming a sheet
that is peated because of the tetrahedral bond angles

The tertiary structure

● Folding of a polypeptide chain into a 3D structure

● Develop because polypeptide is synthesied by the ribosomes
● Most are globular in shape
● Stablised by interactions between R-groups, there are 4 main interactions
● Ionic bonds between positively and negatively charged R-groups
○ Amine groups becomes positively charged by accepting a proton
○ (-NH2 + Ht → -NH3+).
○ Carboxyl groups become positively charged by donating a proton
(-COOH→ -COO + H*).
○ Because of the involvement of protons (hydrogen ions), ionic bonds in
proteins are sensitive to pH changes.
● Hydrogen bonds between polar R-groups.
○ A hydrogen atom forms a link between two electronegative atoms such as
O or N.
○ It is covalently bonded to one of them, wich results in the hydrogen hacing
a slightly positive charge, making it attractive to the other, which as a slight
negative charge
● Disulfide bonds
○ Occurs between pairs of cystenienes
○ This is a covalent bond and the strongest of all the interactions
● Hydrophobic interactions
○ Occur between any of the non–polar R-groups

The effects of the polar and non-polar amino acids on tertiary structure of proteins

Amino acids can be divided into 2 broad categories :

 1. Non-polar and therefore hydrophobic
2. Polar or charged and therefore hydrophillic

- Globular proteins require solubility in water for functioning in cytoplasm or aqueous

environments.

- Hydrophilic amino acids on surface interact with water, while hydrophobic ones cluster
in the core.

- This arrangement stabilizes tertiary structure via maximizing hydrophobic interactions

and hydrogen bonding.

- Proteins in contact with non-polar substances have hydrophobic amino acids on their
surfaces.

- Integral membrane proteins contain hydrophobic amino acids in contact with the
membrane's hydrocarbon core.

- Transmembrane proteins have a hydrophobic belt with hydrophilic regions inside and
outside the cell.

- Channel proteins facilitate diffusion across the membrane's hydrophobic core via a
hydrophilic-lined tunnel.

- Specific hydrophilic ions or molecules pass through channels based on width and
charge distribution.

The quaternary structure

● In proteins that consist of more than a single polypeptide, the three-dimensional

arrangement of subunits is the quaternary structure.
● In a non-conjugated protein, there are only polypeptide subunits. To form the
quaternary structure the polypeptides are linked by the same types of interaction
as in tertiary structure.
● Collagen is another non-conjugated protein. It consists of three polypeptides
wound together to form a rope-like structure with high tensile strength.
● Conjugated proteins have one or more non-polypeptide subunits in addition to
their polypeptides.
● For example, the haemoglobin molecule consists of four polypeptide chains,
each associated with a haem group.
● The inclusion of non-polypeptide components increases the chemical and
functional diversity of proteins.
Globular and fibrous proteins

● The function of a protein depends on its form.

● This can be illustrated by considering the difference between fibrous and globular
proteins.

Globular
● Globular proteins are compact, roughly spherical (circular) in shape and soluble in
water
● Globular proteins form a spherical shape when folding into their tertiary structure
because:
○ their non-polar hydrophobic R groups are orientated towards the centre of
the protein away from the aqueous surroundings and
○ their polar hydrophilic R groups orientate themselves on the outside of the
protein
● This orientation enables globular proteins to be (generally) soluble in water as the
water molecules can surround the polar hydrophilic R groups
● The solubility of globular proteins in water means they play important
physiological roles as they can be easily transported around organisms and be
involved in metabolic reactions
● The folding of the protein due to the interactions between the R groups results in
globular proteins having specific shapes. This also enables globular proteins to
play physiological roles, for example, enzymes can catalyse specific reactions and
immunoglobulins can respond to specific antigens
● Some globular proteins are conjugated proteins that contain a prosthetic group
eg. haemoglobin which contains the prosthetic group called haem

Fibrous
● Fibrous proteins are long strands of polypeptide chains that have cross-linkages
due to hydrogen bonds
● They have little or no tertiary structure
● Due to the large number of hydrophobic R groups fibrous proteins are insoluble in
water
● Fibrous proteins have a limited number of amino acids with the sequence usually
being highly repetitive