An overview of protein structure and classification

1. Proteins are large biological molecules
or macromolecules consisting of one or more chains
of amino acid residues

2. Protein structure
 Biochemists have distinguished four different levels of
the structural organization of proteins i.e., primary,
secondary, tertiary and quaternary
 Primary structure: The sequence of amino acids in a
protein is called primary structure

3. Protein structure
• Secondary structure: The polypeptide chain will be
folded to give a specific conformational form which may be
α-helix and the ß-pleated sheet dependent on hydrogen
bonding
 α-helix: The α-helix is a right-handed coiled strand. The
side-chain substituent of the amino acid groups in an α-
helix extend to the outside. Hydrogen bonds form between
the oxygen of the C=O of each peptide bond in the strand
and the hydrogen of the N-H group of the peptide bond
four amino acids below it in the helix. The hydrogen bonds
make this structure especially stable.

4. Protein structure
 The hydrogen bonding in a ß-sheet is between strands
(inter-strand) rather than within strands (intra-
strand). The sheet conformation consists of pairs of
strands lying side-by-side. The carbonyl oxygens in
one strand hydrogen bond with the amino hydrogens
of the adjacent strand. The two strands can be either
parallel or anti-parallel depending on whether the
strand directions (N-terminus to C-terminus) are the
same or opposite. The anti-parallel ß-sheet is more
stable due to the more well-aligned hydrogen bonds.

5. α-helix

6. ß-sheet

7. Super secondary structure (Motif)
 Secondary structures often group together to form a
specific geometric arrangements known as motifs
 Since motifs contain more than one secondary
structural element, these are referred to as super
secondary structures
 Simple motifs can combine to form more complex
motifs

9. Protein structure
Tertiary structure: The overall three-dimensional
shape of an entire protein molecule is the tertiary
structure
• The protein molecule will bend and twist in such a
way as to achieve maximum stability or lowest energy
state
• Although the three-dimensional shape of a protein
may seem irregular and random, it is fashioned by
many stabilizing forces due to bonding interactions
between the side-chain groups of the amino acids

10. Protein structure
 Under physiologic conditions, the hydrophobic side-
chains of neutral, non-polar amino acids such as
phenylalanine or isoleucine tend to be buried on the
interior of the protein molecule thereby shielding them
from the aqueous medium
 The alkyl groups of alanine, valine, leucine and isoleucine
often form hydrophobic interactions between one-another
 Aromatic groups such as those of phenylalanine and
tryosine often stack together
 Acidic or basic amino acid side-chains will generally be
exposed on the surface of the protein as they are
hydrophilic

11. Protein structure
• The formation of disulfide bridges by oxidation of the
sulfhydryl groups on cysteine is an important aspect of the
stabilization of protein tertiary structure, allowing different
parts of the protein chain to be held together covalently
• Additionally, hydrogen bonds may form between different
side-chain groups. As with disulfide bridges, these
hydrogen bonds can bring together two parts of a chain
that are some distance away in terms of sequence
• Salt bridges, ionic interactions between positively and
negatively charged sites on amino acid side chains, also
help to stabilize the tertiary structure of a protein

12. Tertiary structure

13. Protein structure
 Quaternary structure: Many proteins are made up of
multiple polypeptide chains, often referred to as
protein subunits. These subunits may be the same (as
in a homodimer) or different (as in a heterodimer).
The quaternary structure refers to how these protein
subunits interact with each other and arrange
themselves to form a larger aggregate protein complex.
The final shape of the protein complex is once again
stabilized by various interactions, including hydrogen-
bonding, disulfide-bridges and salt bridges

15. Protein Stability
 Due to the nature of the weak interactions controlling the
three-dimensional structure, proteins are very sensitive
molecules
 The term native state is used to describe the protein in its
most stable natural conformation
 This native state can be disrupted by a number of external
stress factors including temperature, pH, removal of water,
presence of hydrophobic surfaces, presence of metal ions
and high shear
 The loss of secondary, tertiary or quaternary structure due
to exposure to a stress factor is called denaturation
 Denaturation results in unfolding of the protein into a
random or misfolded shape

16. CLASSIFICATION
 Proteins are classified based on their composition, function, and
conformation or structure
 Classification Based on Composition: Simple proteins and
Conjugated proteins
 Simple proteins are those which on hydrolysis yield only amino
acids and no other major organic or inorganic hydrolysis
products
 Conjugated proteins are those which on hydrolysis yield not only
amino acids but also organic or inorganic components. The non-
amino acid part of a conjugated protein is called prosthetic
group. Conjugated proteins are classified on the basis of the
chemical nature of their prosthetic groups e.g., Lipoprotein,
Glycoprotein, Phosphoprotein

17. CLASSIFICATION
 Based on Biological Function:

18. CLASSIFICATION
 Based on Structure: Proteins are classified as Fibrous and Globular
Proteins
 Fibrous proteins consist of polypeptide chains arranged in parallel
along a single axis to yield long fibers or sheets. Fibrous proteins are
insoluble in water. They are the structural elements in the connective
tissue of higher animals. For example, collagen of tendons and bone
matrix, elastin of elastic connective tissue, α-keratin of hair, horn, skin,
nails, feathers, etc.
 Globular proteins consist of polypeptide chains tightly folded into
compact spherical or globular shapes. Most globular proteins are
soluble in aqueous solutions. They have a mobile or dynamic function
in the cell. Of the nearly 2000 different enzymes known to date, nearly
all are globular proteins.
 Some proteins fall between the fibrous and globular types, resembling
fibrous proteins in their long rod-like structures and the globular
proteins in their solubility in aqueous salt solutions. For example,
myosin, an important structural element of muscle and fibrinogen, the
precursor of fibrin, the structural element of blood clots