Functions & structure of

proteins

Biochemistry 1 for Dental student

We will discuss
 . Peptide bond formation
 . Primary, secondary, tertiary and quaternary structure of
proteins
 . Classification of proteins
 Functions of proteinsnctions of proteins
Functions of proteins
 Functions of proteins
 The word protein is derived from Greek word,
“proteios” which means primary. As the name shows,
the proteins are of paramount importance for
biological systems.
 Out of the total dry body weight, 3/4ths are made
up of proteins.
 Proteins are used for body building ; all the major
structural and functional aspects of the body are
carried out by protein molecules. Abnormality in
protein structure will lead to molecular diseases with
profound alterations in metabolic functions
Important biological functions of
proteins
 Many proteins function as enzymes, the biochemical
catalysts. Enzymes catalyze nearly all reactions that occur in
living organisms.
 2. Some proteins bind other molecules for storage and
transport.For example,hemoglobin binds and transports O2
and CO2 in red blood cells and other proteins bind fatty
acids and lipids.
 3. Several types of proteins serve as pores and channels in
membranes, allowing for the passage of small,charged
molecules.
 4. Some proteins, such as collagen, provide support and
shape to cells and hence to tissues and organisms.
 Important biological functions Of proteins
 Mechanical work : Contraction of muscles,, separation of
chromosomes at mitosis
 6. Many proteins play a role in information flow in the cell.
Some are involved in translation whereas others play a role in
regulating gene expression by binding to nucleic acids.
 7. Some proteins are hormones,which regulate biochemical
activities in target cells or tissues; other proteins serve as
receptors for hormones.
 Proteins on the cell surface can act as receptors for various
ligands and as modifiers of cell-cell interactions.
 9. Some proteins have highly specialized functions. For example,
antibodies defend against bacterial and viral infections, and
toxins, produced by bacteria, can kill larger organisms.
Proteins and amino acids
Proteins are polypeptides which are linear
polymers of amino acids linked together by
peptide bonds
 Proteins

Peptide Bond
Proteins are made by polymerization of
amino acids through peptide bonds
 Peptide Bond
 Alpha carboxyl group of one amino acid reacts with alpha
amino group of another amino acid to form a peptide bond
or CO-NH bridge
 . Two amino acids are combined to form a dipeptide.
 Three amino acids form a tripeptide.
 Four will make a tetrapeptide.
 A few amino acids together will make an oligopeptide.
 Combination of 10 to 50 amino acids is called as a
polypeptide.
 Big polypeptide chains containing more than 50 amino
acids are called proteins.
Peptide Bond
Peptide Bond
 Numbering of Amino Acids in
Proteins
 . In a polypeptide chain, at one end there will be one free
alpha amino group. This end is called the amino terminal
(N-terminal) end and the amino acid contributing the alpha-
amino group is named as the first amino acid.
 The other end of the polypeptide chain is the carboxy
terminal end (C-terminal), where there is a free alpha
carboxyl group which is contributed by the last amino acid.
All other alpha, amino and alpha carboxyl groups are
involved in peptide bond formation
 Usually the N-terminal amino acid is written on the left hand
side when the sequence of the protein is denoted. In
nature, the biosynthesis of the protein also starts from the
amino terminal end.
Numbering of Amino Acids in
Proteins
STRUCTURE OF PROTEINS
(ORGANIZATION OF PROTEINS)

 Proteins have different levels of

structural organization;
 primary,
 secondary,
 tertiary
 quaternary
 Protein Structure

Primary Assembly
STRUCTURE

PROCESS
Secondary Folding

Tertiary Packing

Quaternary Interaction
Protein Structure
Protein Structure
The linear sequence of amino acid residues defines
the primary structure.
 Primary Structure
 Primary Structure; Sequence
 Primary structure denotes the number and sequence of amino
acids in the protein. The higher levels of organisation are
decided by the primary structure.
 Each polypeptide chain has a unique amino acid sequence
decided by the genes
 . The following example may be taken to have a clear idea of

the term "sequence".

 1. Gly - Ala - Val
2. Gly - Val - Ala Both the tripeptides shown above contain the
same amino acids; but their sequence is altered. When the
sequence is changed, the polypeptide is also different
. The primary structure is maintained by the covalent bonds of
the peptide linkages
 Secondary Structure of Proteins
 The term "secondary structure" denotes the configurational
relationship between residues which are about 3–4 amino
acids apart in the linear sequence.
 Secondary and tertiary levels of protein structure are
preserved by noncovalent forces or bonds like hydrogen
bonds, electrostatic bonds
 Secondary Structure
 non-linear
 3 dimensional
 formed and stabilized by
hydrogen bonding,
Secondary structure

α-helix β-sheet

Secondary structures, α-helix

and β-sheet, have regular
hydrogen-bonding patterns.
 Alpha-helix
 The alpha-helix is a spiral structure The
polypeptide bonds form the back-bone and the
side chains of amino acids extend outward.
 The structure is stabilized by hydrogen bonds
between NH and C=O groups of the main
chain.
 Each turn is formed by 3.6 residues.
 . In proteins like hemoglobin and myoglobin,
the alpha-helix is abundant. The alpha-helix is
the most common and stable conformation for
a polypeptide chain.
Beta-pleated Sheet
 The polypeptide chains in beta-pleated sheet is
almost fully extended
 It is stabilized by hydrogen bonds between NH and
C=O groups of neighboring polypeptide segments
but the same polypeptide.
 Beta-pleated sheet is the major structural motif in
proteins like silk fibroin and carbonic anhydrase
 Tertiary structure

The two secondary structure

Domain
 Completely folded polypeptide chain
Interactions of side chains (mostly hydrophobic)
 tertiary structure
 The tertiary structure denotes three-dimensional structure of
the whole protein. The tertiary structure is maintained by
hydrophobic bonds, electrostatic bonds
 Quaternary structure
.

 Association of subunits (polypeptide chains)

 Noncovalent interactions (hydrophobic)
 Quaternary Structure
 Quaternary structure results when the proteins consists of
two or more polypeptide chains( subunits ) are held
together by non-covalent forces.
 Each polypeptide chain is termed as subunit or monomer

 The protein will lose its function when the subunits are

dissociated.
 . Depending on the number of monomers (subunits), the

protein may be termed as dimer (2), tetramer (4), etc.

 . For example:

2 alphachains and 2 beta-chains form the Hemoglobin

molecule;
2 heavy chains and 2 light chains combine to form one
molecule of immunoglobulin G.
Definitions of levels of
organization
 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.
 3. Tertiary structure denotes the overall
arrangement and inter-relationship of the various
regions, or domains of a single polypeptide chain.
 4. Quaternary structure results when the proteins
consists of two or more polypeptide chains are held
together by non-covalent forces
Protein Structure
Structure-Function Relationship
 The three-dimensional structural
conformation provides and maintains the
functional characteristics.
 The three-dimensional structure, in turn, is
dependent on the primary structure. So, any
difference in the primary structure may
produce a protein which cannot serve its
function.
 Hemoglobin
 It is the transporter of oxygen is a tetrameric
protein, with each monomer having a heme unit
Binding of oxygen to one heme facilitates oxygen
binding by other subunits. Binding of H+ and CO2
promotes release of O2 from hemoglobin.
 Even a single amino acid substitution alters the
structure and thereby the function. For example, in
sickle cell anemia (HbS), the 6th amino acid in the
beta chain is altered from normal glutamic acid to
abnormal valine. This leads to profound clinical
manifestations
Collagen
 It is the most abundant protein in mammals and is
the main fibrous component of skin, bone, tendon,
cartilage and teeth.
 Collagen forms a superhelical cable where the 3
polypeptide chains are wound around
 In collagen, every third residue is a glycine. The
only amino acid that can fit into the triple-stranded
helix is glycine. The quarter staggered triple-helical
structure of collagen is responsible for its tensile
strength.
 Collagen
 It is the major protein component of calcifying tissues like bone, dentin and
cementum.
 . Each polypeptide chain of collagen has about 1000 amino acid
residues.
 About 30% of the amino acids are glycine.
 Proline and lysine constitute another 30%.
 Proline and lysine residues are later hydroxylated to form hydroxyproline
and hydroxylysine, which are further glycosylated
 Hydroxyproline and hydroxylysine residues are formed when specific proline
residues and lysine are hydroxylated after incorporation into the
polypeptide chains of collagen. The hydroxylation reactions are catalyzed
by enzymes and require ascorbic acid (vitamin C).Hydroxylation is impaired
in the absence of vitamin C,and the triple helix of collagen is not assembled
properly.
 .
 Classification of protein Based on shapes

Active site
cleft
Globular proteins

• Enzymes & regulatory proteins

•These are usually soluble in water or
in aqueous media containing acids,
bases, salts or alcohol, and diffuse
readily Hemoglobin Enzyme

Fibrous proteins
• Structural proteins : support
are insoluble in all common solvents
•

such as water, dilute acids, alkalies Collagen

and salts and also in organic
solvents.
 Globular proteins

These are usually soluble in water or in

•

aqueous media containing acids, bases, salts or

alcohol, and diffuse readily
 Fibrous proteins
 I .Collagen is the major proteins of white connective tissues (tendons*,
cartilage) and of bone and teeth . More than half the total protein in
mammalian body is collagen unique in containing high contents (12%) of
hydroxyproline, Hydroxyproline residues are formed when specific proline
residues are hydroxylated after incorporation into the polypeptide chains
of collagen. The hydroxylation reactions are catalyzed by enzymes and
require ascorbic acid (vitamin C).Hydroxylation is impaired in the
absence of vitamin C,and the triple helix of collagen is not assembled
properly.
 II. Elastins. Is the major constituents of yellow elastic tissues (ligaments,
blood vessels); differ from collagens in not being converted to soluble
gelatins.
 III. Keratins is the major constituents of epithelial tissues (skin, hair,
nails); usually contain large amounts of sulfur in the form of cystine–
human hair has about 14% cystine.
 Isoelectric pH (pI) of Proteins
 At the isoelectric point, the number of anions and
cations present on the protein molecule will be equal
and the net charge is zero
 At the pI value, the proteins will not migrate in an
electrical field; solubility, buffering capacity and
viscosity will be minimum and precipitation will be
maximum.
 On the acidic side of pI, the proteins are cations and
on alkaline side, they are anions in nature. iv
Functions of proteins
 Functions of proteins
 Catalytic proteins, e.g. enzymes
 ii. Structural proteins, e.g. collagen, elastin, keratin
 iii. Contractile proteins, e.g. myosin, actin, flagellar
proteins iv.
 Transport proteins, e.g. hemoglobin, myoglobin,
albumin, transferrin
 v. Regulatory proteins or hormones, e.g. ACTH,
insulin, growth hormone vi.
 Genetic proteins, e.g. histones
 vii. Protective proteins, e.g. immunoglobulins,
clotting factors.
 Storage protein , e.g ferritin
CLASSIFICATION OF PROTEINS
Proteins may be divided into three major
groups:
 simple

 conjugated

 derived
 . Simple Proteins
According to definition, they contain only amino acids. But they
also contain very small quantity of carbohydrates.
Albumins

 Globulins
 Conjugated Proteins
They are combinations of protein with a non-protein part, called
prosthetic group Conjugated proteins may be classified as
follows:
1-Glycoproteins
2-Lipoproteins.
3-Chromoproteins
4-Phosphoproteins.
5-Metalloproteins
 Conjugated Proteins
1-Glycoproteins: These are proteins combined with
carbohydrates.
Hydroxyl groups of serine or threonine and amide groups of

asparagine and glutamine form linkages with carbohydrate

residues.
When the carbohydrate content is more than 10% of the

molecule, the viscosity is correspondingly increased

they are sometimes known as mucoproteins or proteoglycans.

Blood group antigens and many serum proteins are

glycoproteins.
 Conjugated Proteins
2-Lipoproteins: These are proteins loosely combined with lipid
components. They occur in blood and on cell membranes.
Nucleoproteins: These are proteins attached to nucleic acids,
e.g. Histones. The DNA carries negative charges, which
combines with positivelycharged proteins.
3-Chromoproteins: These are proteins with coloured prosthetic
groups. Hemoglobin (Heme, red
4-Phosphoproteins: These contain phosphorus. examples
Casein of milk. The phosphoric acid is added to the hydroxyl
groups of serine and threonine residues of proteins.
5-Metalloproteins: They contain metal ions. Examples are
hemoglobin (iron), cytochrome (iron), tyrosinase (copper) and
carbonic anhydrase (zinc).
 Derived Proteins
Derived Proteins They are degradation products of native
proteins. Denaturation is the first step, which has been
discussed previously. Progressive hydrolysis of protein results in
smaller and smaller chains: protein ,peptones ,peptides ,amino
acids.
 Classification Based on Nutritional Value
1. Nutritionally Rich Proteins They are also called as complete
proteins or first class proteins. They contain all the essential
amino acids in the required proportion. On supplying these
proteins in the diet, the young individuals will grow
satisfactorily. A good example is all animal protein (casein of
milk )
2. Incomplete Proteins They lack one essential amino acid.
They cannot promote body growth in young individuals; but
may be able to sustain the body weight in adults. Proteins from
pulses are deficient in methionine, while proteins of cereals lack
in lysine. If both of them are combined in the diet, good growth
could be obtained.
3- Poor Proteins They lack in many essential amino acids and a
diet based on these proteins will not even sustain the original
body weight. corn lacks tryptophan and lysine.