ORGANIZATION OF PROTEINS
(STRUCTURE OF PROTEIN)
SAM OLERIMI (MBBS)
• The term protein is generally used for a
polypeptide containing more than 50 amino
acids.
• Proteins are the polymers of L-α-amino acids
are folded polypeptides.
• Each Protein has a three dimensional structure.
• Majority of proteins are compact and highly
convoluted molecules.
• The structure of proteins are rather complex
which can be divided into 4 levels of
organization
Why is Protein Structure
So Important?
• Protein structure dictates function.
• Sometimes a mutation in DNA results in an amino acid
substitution that alters a protein’s structure and compromises
its function
– Example: Hemoglobin-S leading to sickle-cell anemia
• One amino acid substitution results in the abnormal
beta chain in HbS molecules. Instead of glutamate,
valine was added at the sixth position of the
polypeptide chain.
• Normally rounded red blood cells are converted into
sickle shapes.
1. Primary structure of protein means the order
of amino acids in the polypeptide chain
2. Secondary structure is the steric relationship of
amino acids, close to each other thus polypeptide
chain form sheets and coils.
3. Tertiary structure denotes the overall
arrangement and inter-relationship of the various
regions, or domains of a single polypeptide chain
i.e. sheets and coils packs into functional domains.
4. Quaternary structure results when the proteins
consist of two or more polypeptide chains held
together by non covalent forces.
NH2
Lysine
Histidi
n
Valine
Argini
ne
Alanin
e
COOH
PRIMARY STRUCTURE
• The primary structure denotes the number and sequence
of amino acids in the protein.
• The numbers of amino acids vary
(e.g. insulin 51, lysozyme 129, haemoglobin 574, gamma
globulin 1250).
• Each polypeptide chain has a unique amino acid
sequence decided by the genes.
• The primary structure is maintained by the covalent
bonds of the peptide linkages.
• Polar amino acids (hydrophilic) tend to be placed on the
outside of the protein.
• Non-polar (hydrophobic) amino acids tend to be placed
on the inside of the protein
• The number of possible sequence of amino acid in the
primary structure is infinite.
SECONDARY STRUCTURE
• This denotes the configurational relationship between
residues which are bout 3-4 amino acids apart in linear
sequence
• The secondary and tertiary levels of protein structure
are preserved by non-covalent forces or bonds like
hydrogen bonds, electrostatic bonds, hydrophobic
interactions and van der Waals forces.
• Polypeptide chains tend to twist or coil upon
themselves.
• Each amino acid is spatially(closely) related to its
neighbour in the same way.
• It may take any form either α-Helix or β pleated sheet
STRUCTURE OF α-HELIX
• The folding of the polypeptide chain occurs
using weak hydrogen bonds
Properties of alpha helix
• It is clockwise , spiral
• First -NH and last C=O groups at the ends of
helices do not participate in H-bond
• Ends of helices are polar, and almost always at
surfaces of proteins
• Always right- handed because proteins have L-
amino acids.
• More stable form.
• Easily stretchable.
STRUCTURE OF β-PLEATED SHEETS
• This produces the beta pleating
• The length of the helix or pleat is determined
by the number of amino acids .
PROPERTIES OF β-PLEATED SHEETS
• The peptide strands may run in the same
direction (Parallel strands)or may be
( anti-parallel strands).
• They are in elastic because the H bonds are at
right angles to the direction of stretching.
TERTIARY STRUCTURE
• The folding of the polypeptide and refolding on itself, give
rise to a definite three dimensional confirmation which
makes it globular and rigid structure.
• This folding is held together by
strong covalent bonds (e.g. cysteine-cysteine disulphide
bridge)
The weak interactions include:
Hydrogen bonds among polar side chains
Ionic bonds between charged R groups ( basic and acidic
amino acids)
Hydrophobic interactions among hydrophobic ( non polar)
R groups.
Stabilizing Cross-Links
• Cross linkages can be between 2 parts of a protein
or between 2 subunits
• Disulfide bonds (S-S) form between adjacent -SH
groups on the amino acid cysteine
Formation of Binding Site
• The binding site forms when amino acids from
within the protein come together in the folding
• The remaining sequences may play a role in
regulating the protein’s activity
QUATERNARY STRUCTURE
• The quaternary protein structure involves the
clustering of several individual peptide or protein
chains into a final specific shape. Bonding
interactions including hydrogen bonding, salt
bridges, and disulfide bonds hold the various
chains into a particular geometry.
• Refers to the organization of subunits in a protein
with multiple subunits, may be identical or
different. Subunits have a defined arrangement
held together by weak, non-covalent interactions
(hydrophobic, H bonds, ionic bonds) .
• There are two major categories of proteins
with quaternary structure - fibrous and
globular
• Fibrous proteins such as the keratins in wool
and hair.
• Examples of Globular proteins include insulin
and hemoglobin.
• Structural and functional advantages of
quaternary structure
Stability: reduction of surface to volume ratio
Bringing catalytic sites together
Biology/Chemistry of Protein Structure
Primary Assembly
STRUCTURE
PROCESS
Secondary Folding
Tertiary Packing
Quaternary Interaction
Protein Structure
Primary structure (Amino acid sequence)
↓
Secondary structure （ α-helix, β-sheet ）
↓
Tertiary structure （ Three-dimensional structure
formed by assembly of secondary structures ）
↓
Quaternary structure （ Structure formed by many
polypeptide chains ）
