Proteins

PROTEINS
 Proteins are the most abundant biological
macromolecules, occurring in all cells and all parts of cells.
 Proteins also occur in great variety; thousands of different kinds,

ranging in size from relatively small peptides to huge

polymers with molecular weights in the millions, may be found
in a single cell.
 Moreover, proteins exhibit enormous diversity of biological

function and are the most important final products of

the information pathways.
- Proteins are made up of large numbers of amino acids
linked into chains by peptide bonds joining the carboxyl
group of one amino acid to amino group of the next.

- The number of amino acids present varies from about

a hundred to several thousands in different proteins.

- Some proteins are composed of only one polypeptide

chain while others are composed of two or more
polypeptide chains (multisubunit proteins) held
together by non-covalent bonds
 The general properties
of proteins
1. High molecular weight substances.
2. It constitutes more than 50% of the dry weight of the cell.
3. It presents in different shapes; fibrous and globular.
4. The globular is soluble in water and diluted salt solution with
different degrees
5. The chemical and physical properties depend on the amino
acids
forming the protein.
6. The biological properties and 3D conformation depend also
on the constituting amino acids.
7. All proteins are amphoteric compounds.
8. They precipitate by heat, in alcohols and in their isoelectric
 Amino Acid
R Group
Carboxyl
Amino Group Group

Central Carbon
 Amino Acids
 There are 20 different types of amino
acids used in making proteins.
Amino Acids: Building Blocks of
Proteins
 A peptide bond is a covalent bond
formed.

 Polypeptides are polymers of amino

acids linked together by peptide bonds,
with the amino group of one acid joining
the carboxyl groups of its neighbor.
Amino Acids: Building Blocks of
Proteins
Amino Acid Amino Acid
R R

H N C C OH H N C C OH

H H O H H O

H2O

Dipeptide
R R

H N C C N C C OH

H H O H H O
 Classification of
proteins
Proteins can be classified according to three different
criteria:
A) proteins can be classified on the basis of the chemical
composition.

B) proteins can be classified on the basis of shape.

C) proteins can be classified on the basis of their biological

function.
 Classification of
proteins
a- According to their chemical composition:
Proteins can be classified on the basis of their
chemical composition into two main classes:

1- Simple proteins 2-
conjugated proteins

1- Simple proteins:
are those proteins which upon hydrolysis give only amino
acids.
Example: ribonuclease A, chymotrypsin.
 2- Conjugated proteins:
are proteins which yield upon hydrolysis amino acids
and non-protein part is called the prosthetic
group.

-Conjugated proteins are classified on the basis of the

chemical nature of their prosthetic groups:
i) nucleoproteins
ii) Glycoproteins (contains carbohydrate part)
iii) Lipoproteins (contains lipid part)
iv) Hemoproteins (contains heme)
v) Metalloproteins (contains metal)
vi) Phosphoproteins (phosphorylated protein)
Examples of conjugated proteins
 Classification of proteins
b- According to their shape

Proteins can be classified on the basis of their chemical

composition into two main classes:

1- Globular proteins 2- Fibrous

proteins

1- Globular proteins:
- They are generally soluble in water.
- The polypeptide chains are tightly folded into a globular
shape.
Example:
2- Fibrous proteins:
- They are insoluble in water
- Their polypeptide chains are arranged in long strands
(elongated in the form of fibers).
Example:
Collagen, elastin, keratin
 Classification of
proteins
c. According to their biological function

Proteins can be classified on the basis of their biological function

into:
1 Catalytic function (enzymes)
2 Transport function (hemoglobin, albumin, transferrin)
3 Nutrient and storage proteins [e.g., casein & ferritin]
4 contractile or mobile proteins [e.g., actin, myosin]
5 Structural function [Keratin, elastin, collagen]
6 Defense proteins [e.g., immunoglobulins,
fibrinogen and thrombin]
7 Regulatory function, some hormones are proteins
(Growth hormone [GH, somatotropin])
8 Some toxins are proteins
9 Defense (Antibodies and coagulating factors)
 Protein
synthesis
The relation between DNA, RNA & proteins
 The flow of information from DNA to RNA to protein is
termed the “central dogma”.
 The genetic information corresponding to certain protein is
stored in the form of nucleotide sequence in DNA called gene.
 The gene is transcribed in the nucleus into the specific
nucleotide sequence called mRNA molecule than contains the
genetic code.
 mRNA is translated in the cytoplasm by the ribosome which
bind the aminoacids charged in tRNA in a sequence determined
Central Dogma of Molecular Genetics
 Genetic
code
 Each amino acids has at least one code in the mRNA, some has
6
codons.
Transcription and Translation
 Protein structure
The amount and type of amino acids found in a protein
and the sequence in which they are arranged in the
polypeptide chains is a unique characteristic of each
protein.

- The amino acid sequence of a number of proteins has

been determined and it is established that the sequence of
amino acids is the force that determines the protein
conformation, which in turn is responsible for the
biological function of protein.
 Protein structure
Protein structure can be considered at four levels:
1) Primary structure
2) Secondary structure
3) Tertiary structure
4) Quaternary structure
Note:
- All proteins have their own specific primary structure, amino acids
sequence, determined by their genes
- Different proteins have different extent of secondary structure.
Some have
none.
- All intracellular globular proteins have a tertiary structure.
- Proteins made of more than one subunit [polypeptide] have
-Primary structure

- Secondary structure

- Tertiary structure

- Quaternary structure
 Forces that stabilize the different
protein structures

Level Interactions that stabilize the structure

Primary Covalent bond (amide/peptide bond)
Secondary Hydrogen bonds (C=O with NH) to form -helix and -sheet
Ionic bonds,
disulfide bonds,
Tertiary hydrophobic interactions,
hydrogen bonding
(between R groups in
the same chains)
Ionic bonds,
disulfide bonds,
Quaternary hydrophobic interactions,
hydrogen bonding (between R groups in different chains)
 Amino Acid Amino Acid
R R

H N C C OH H N C C OH

H H O H H O

H2O

Dipeptide
R R

H N C C N C C OH

H H O H H O 26
 Primary
The simplest level of structure
protein structure, primary
structure is simply the sequence of amino
acids in a polypeptide chain.
The hormone insulin has two polypeptide chains
A, and B. The sequence of the A chain, and the
sequence of the B chain can be considered as an
example for primary structure.
 Secondary
structure
secondary structure, refers to local folded structures that form
within a polypeptide due to interactions between atoms.
The most common types of secondary structures are the α helix
and the β pleated sheet. Both structures are held in shape by
hydrogen bonds, which form between the carbonyl O of one
amino acid and the amino H of another.

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α-Helix

10
α-Helix as viewed from one end

11
A space feeling model of α- Helix

12
 -Sheet
-pleated sheet consists of peptide chains
arranged side by side which resembles a
piece of paper folded into many pleats

– Like a helix, the -sheet uses the full H-

bonding capacity of the polypeptide
backbone

– HOWEVER, H-bonding occurs BETWEEN

neighboring peptide chains, rather than
within one.

13
-Sheet

14
-Sheet

15
 Secondary
structures…
• Helices and sheets can be combined in
various ways

• Some proteins have mainly a-helices,

some have mainly b-sheets, but most
have both

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 Secondary structure:
fibrous proteins
• Water insoluble
• Usually physically tough
• Usually static: provides mechanical
support to individual cells and entire
organisms
• E.g., collagen, keratin

18
Examples of secondary
structure…

19
Examples of secondary
structure…

20
Examples of secondary
structure
The collagen triple helix. Left-
handed polypetide helices are
twisted together to form a right-
handed superhelical structure.

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 Tertiary structure
The overall three-dimensional structure of a
polypeptide is called its tertiary structure.

The tertiary structure is primarily due to

interactions between the R groups of the
amino acids that make up the protein.
Important to tertiary structure are hydrophobic
interactions, in which amino acids with nonpolar,
hydrophobic R groups cluster together on the
inside of the protein, leaving hydrophilic amino
acids on the outside to interact with surrounding
water molecules.
Also, Disulfide bonds, covalent linkages between
the sulfur-containing side chains of cysteines, are
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much stronger than the other types of bonds that
contribute to tertiary structure
• Refers to the complete three dimensional
structure of entire polypeptide. Usually
involves the packing of structural
elements (a-helix, b- pleated sheet, etc.)
 Tertiary structure:
•
globular
Structurally complex
proteins
• Usually dynamic
• Usually compact (tightly folded), roughly
spherical
• Can be water-soluble
– If so, characteristically have hydrophobic
interior and hydrophilic surface
• Can be water-insoluble (e.g., bound to
biological membrane)

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Examples of Tertiary
structure…

myoglobin
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Examples of Tertiary structure…
Examples of Tertiary structure…
Examples of Tertiary structure…
 Quaternary structure
When multiple polypeptide chain subunits come
together, then the protein attains its quaternary
structure.
An example for quaternary structure is hemoglobin.
The hemoglobin carries oxygen in the blood and is
made up of four subunits, two each of the α and β
types.
 Quaternary
structure of
proteins

Nitritite reductase E. Coli fumarase

Human hemoglobin Bacterial methane hydroxylase

 Folding, unfolding and misfolding
of protein
• A protein that is folded into its normal
physiologically active chain conformation is in
its native state.

• Denaturation occurs when a native protein unfolds

owing to cleavage of disulfide bridges or
disruption of the weak attractive forces. It may be
reversible or irreversible.

• Protein can be denatured by heat, extremes of

pH, certain organic solvents such as alcohol,
acetone, certain solute like urea, or by exposure
of the protein to detergents.
Denatured proteins are usually non-functional
 Protein misfolding and diseases
• There are at least 15 human diseases in which
amyloid fibers accumulate (as a result of
misfolding of proteins).

• Amyloid diseases result in a variety of different

clinical presentations, including Alzheimer’s
disease.

• All the proteins involve in these diseases

undergo conformational alteration to a
common structure in the amyloid fibril.