PROTEINS

Proteins are complex macromolecules composed of amino acids that play crucial roles in
biological processes. Proteins constitute more than 50% of the dry weight of a cell. Proteins are
formed from peptide bond formation resulting in the loss of H2O molecule joining of amino acids
to form peptide chains. The “backbone” of a protein consists of -N-Cα- C-. Generally, peptides are
short chains of amino acids linked together by peptide bonds. They are smaller than proteins,
typically composed of 2 to 50 amino acids

When proteins contain a single polypeptide, they are called monomeric proteins but if the protein
contains more than one polypeptide, it is a multimeric protein. If a multimeric protein contains
same type of polypeptide, it is termed homomultimeric protein, where the multimeric protein is
constituted by different type of polypeptides, they are called heteromultimeric proteins.

Classification of Proteins
Proteins are classified based on various criteria, including their composition, structure, and
function.
A. Classification by Composition
➢ Simple Proteins: Contain only amino acids (e.g., albumins, globulins).
➢ Conjugated Proteins: Contain a protein component and a non-protein part called a
prosthetic group (e.g., glycoproteins, lipoproteins, metalloproteins).
B. Classification by Structure
➢ Fibrous Proteins: Have elongated, fiber-like structures, providing structural support and
strength. They are generally insoluble in water. Examples include collagen, keratin, and
elastin.
➢ Globular Proteins: Have compact, spherical shapes and are usually soluble in water. They
are often involved in metabolic processes. Examples include enzymes, hemoglobin, and
antibodies.
C. Classification by Function
➢ Structural Proteins: Provide support and shape (e.g., collagen in connective tissues).
➢ Enzymatic Proteins: Catalyze biochemical reactions (e.g., amylase, protease).
➢ Transport Proteins: Carry substances across cell membranes or within the bloodstream
(e.g., hemoglobin, albumin).
➢ Hormonal Proteins: Act as chemical messengers (e.g., insulin, growth hormone).

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 ➢ Defensive Proteins: Protect the body from disease (e.g., antibodies).
➢ Storage Proteins: Store essential nutrients (e.g., ferritin stores iron).
➢ Contractile Proteins: Aid in muscle contraction and movement (e.g., actin, myosin).

Molecular Structure of Protein

Proteins present different levels of organization represented by their Primary, Secondary, Tertiary
and the Quaternary structures.

Primary Structure of Protein

This refers to the number of amino acids present in the protein and their positions in the particular
protein. The positioning of amino acids that determines the sequence is the determinant of the of
the conformation, properties and functionality of the protein. Alterations in the positions of the
amino acids of a protein will affect the functions and may make the protein inactive.

Secondary Structure of Protein

The secondary structure refers to localized folding patterns within a polypeptide chain, stabilized
by hydrogen bonds between the backbone amide and carbonyl groups. This explains the regular
spatial and repetitive arrangement of the polypeptide chains of protein, which are held together by
hydrogen bonds.

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 α Helix: The polypeptides in their secondary structure are arranged coiling on a central axis
maintained by hydrogen bonds formed from the reaction of N of the amino moiety and the oxygen
of the carbonyl group. The hydrogen bonds are formed every four residues in the protein and are
responsible for the coil. It is known that hydrogen bonds are weak, but the large numbers found in
the helix makes the protein very stable and compact. The presence of proline, arginine, lysine and
glutamate located close together will affect the spatial arrangement of the polypeptide prevent the
formation of helices.

β Sheet: The sheet occurs when two or more polypeptide chains are paired, they can establish
hydrogen bonds between the amino groups of one chain and the carboxyl groups of the other
polypeptide to form lamellar structures with pleated structure. The paired polypeptide may be
parallel or anti parallel.

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Usually most globular proteins exist in the helical form while fibrous proteins as sheets. However,
globular proteins generally have α helix segments, β pleated sheet and random coils.

Tertiary Structure of Protein

This describes the three-dimensional structure of protein that defines the function. At this level a
protein could be classified as fibrous of globular. Fibrous proteins are clearly defined by the
secondary structure which is sufficient to shape its conformation. On the other hand, though
globular proteins can adopt the α helix segments, β pleated sheet structures, they still contain
segments that are randomly arranged and provide the folds needed for protein to achieve the native
conformation and functionality.

The three-dimensional structure of globular proteins is maintained via the interactions between the
side chains of the amino acid constituents. Proteins are most stable at its native conformation,
where it exists at its lowest free energy. The tertiary structure of proteins is maintained by a number
of interactions and forces.
Stabilizing Interactions for Tertiary Structure:
i. Hydrogen Bonds: Between polar side chains.
ii. Ionic Bonds: Between oppositely charged side chains.
iii. Hydrophobic Interactions: Nonpolar side chains tend to cluster in the interior of the
protein, away from water.

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 iv. Van der Waals Forces: Weak attractions between all atoms in close proximity.
v. Disulfide Bridges: Covalent bonds between cysteine residues, adding stability to the
folded structure.

Forces maintaining the tertiary structure of a polypeptide chain. I. Electrostatic attractions. II. Hydrogen bond. III.
Interactions of nonpolar groups. IV. Disulfide bond. V. Hydrophilic groups oriented outwards (Source: Modified from Anfinsen).

Quaternary Structure of Protein

The quaternary structure arises when two or more polypeptide chains (subunits) associate to form
a functional protein complex. Not all proteins have a quaternary structure—only those that are
multimeric.

Types of Subunit Arrangement:

➢ Dimer: Two subunits (e.g., HIV protease).

➢ Tetramer: Four subunits (e.g., hemoglobin).

➢ Multimer: Larger complexes with multiple subunits (e.g., ribosome).

The stabilizing interactions is similar to tertiary structure interactions, including hydrogen bonds,
ionic interactions, and hydrophobic forces.

Each structural level is essential for the protein’s stability and biological activity. Misfolding at
any level can lead to dysfunctional proteins and, potentially, diseases like Alzheimer’s or cystic
fibrosis.

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Denaturation and Renaturation: Proteins can lose their structure and function due to changes in
temperature, pH, or chemical environment, known as denaturation. Under certain conditions, they
can refold (renaturation), but sometimes, denaturation is irreversible.

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