Welcome to class of
Proteins
Dr. Meera Kaur
Learning Objectives
• To understand:
• The functions of protein as an important biomolecule
• Different structures of proteins
• Structures of two peptide chains conformations: alpha helix and
beta pleated sheet
• The concept of folding, unfolding and misfolding of protein
• The deficiency and excess of proteins in human nutrition
Introduction...
• Proteins are the most important
macromolecules in living cells. The word
protein is derived from the Greek protos,
meaning ‘first’ or ‘foremost’
• Almost everything that occurs in the cell
involves one or more protein
• Amino acids are the building blocks of
proteins
Introduction
• In a protein molecule many peptide chains
join together to form a polypeptide chain
• Proteins performs many functions in living
organism
• Proteins may be classified according to their
physiologic functions
Classifications of proteins
Nutritional quality
- Complete
- Partially Complete
- Incomplete OR
- Protein of high BV
- Supplementary
- Protein of low BV
Physiological functions
- Enzymes
- Nutrient and Storage proteins
- Contractile or Motile proteins
- Structural proteins
- Defense proteins
- Regulatory proteins
- Transport proteins
- Other proteins
Functions of proteins…
• Enzymes: The most valid and the most highly specialized
proteins are those with catalytic activity – the enzymes. All the
chemical reactions of organic biomolecules in cells are catalyzed
by enzymes.
• Transport proteins: These proteins in blood bind and carry
specific molecules or ions from one organ to another, e.g.
Hemoglobin, lipoprotein
• Nutrient and storage proteins: The seeds of many plants
store nutrient proteins required for the growth of germinating
seedling, e.g. seed protein of corn, rice and wheat. Ovalbumin,
the protein of egg white and casein the protein of milk are other
examples of nutrient proteins. The ferritin found in some bacteria
and in plant and animal tissues stores iron.
Functions of proteins…
• Contractile or motile proteins: Some proteins endow cells and
organisms with the ability to contract, change shape, or move about.
Actin and myosin function in the contractile system of skeletal muscle
and in many other cells.
• Structural proteins: Many proteins serve as supporting filaments,
cables, or sheets to give biological structures, strength or protections.
The major component of tendons and cartilage is the fibrous protein
of collagen, which has very high tensile strength. Leather is almost
pure collagen. Hairs, fingernails and feathers consist of the tough,
insoluble protein keratin. The major component of silk fibers and
spider webs is fibroin.
• Defense proteins: Many proteins defend organism against invasion
by other species or protect them from injury. The immunoglobulins or
antibodies, the specialized proteins made by the lymphocytes of
vertebrates can recognize and precipitate or neutralize invading
bacteria, viruses or foreign proteins of another species. Fibrinogen
and thrombin are blood-clotting factors that prevent loss of blood
when the vascular system is injured.
Functions of proteins
Regulatory proteins: Some proteins help regulate cellular or
physiological activities, e.g. Insulin, a hormone regulates the
metabolism of sugars. Other regulatory proteins bind to DNA and
regulates the biosynthesis of enzymes and RNA molecules,
involved in cell division in both prokaryotes and eucaryotes.
Other proteins: There are numerous other proteins whose
functions are rather exotic and not easily classified, e.g.,
monellin, a protein of an African Plant, has an intensely sweet
taste. It is being studied as a nontoxic food sweetener for human
use
All these proteins with their very different properties and functions
are made from the same group of 20 amino acids.
A gallery of protein structure and function…
A gallery of protein structure and function…
A gallery of protein structure and function…
A gallery of protein structure and function
Properties of proteins
• Proteins are very large molecules
• Proteins have characteristics amino acid composition
• Some proteins contain chemical groups other than
amino acids
• Protein can be separated and purified
• Individual proteins can be quantified
• The functions of a protein depend on its amino acids
sequence
• The amino acid sequence of polypeptides chain can
be determined
• Homologous proteins from different species have
homologous sequences
Structures of proteins
• Simple proteins are made up of peptide bond
• Conjugated proteins have structures which
incorporate non protein portions called prosthetic
group
• The peptide chains of a particular protein molecule
are folded in the same way. This is known as chain
conformation
• The unique chain conformation of a given protein is
influenced by many week forces (disulfide bridges,
ionic bond, hydrogen bond, etc.)
Levels of protein structure…
Primary
Secondary
Tertiary
Quaternary
Levels of protein structure
Primary structure
• Amino acid sequence of polypeptide chain
• Some consider that primary structure also includes
number and location of any disulphide bonds
Secondary structure…
• Refers to regular recurring arrangements in space of
adjacent amino acid residues in a polypeptide chain.
• Most common types of secondary structures: a-helix
and b-pleated sheet
Secondary structures…
In some proteins, the regions of peptide chains are coiled into a
spiral shape called an -Helix
– -Helix is a right-handed helix. The helixes are joined
together by intra-chain H-bonds formed between the
carbonyl oxygen of one amino acid residue and the N-H
hydrogen of the fourth residue down the chain.
– R-groups protrude outward from helical backbone
– Core of the helix is tightly packed
-Helix
-Helix as viewed from one end
A space feeling model of - Helix
Secondary structures…
b-pleated sheet consists of peptide chains arranged
side by side which resembles a piece of paper folded
into many pleats
– Like a helix, the b-sheet uses the full H-bonding
capacity of the polypeptide backbone
– HOWEVER, H-bonding occurs BETWEEN
neighboring peptide chains, rather than within
one.
– R-groups extend above and below the plane of
the sheet
Sheet…
-Sheet
Pleat of -Sheet
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
Secondary structure: fibrous proteins
• Water insoluble
• Usually physically tough
• Usually static: provides mechanical support to
individual cells and entire organisms
• E.g., collagen, keratin
Examples of secondary structure…
Examples of secondary structure…
Examples of secondary structure
The collagen triple helix. Lefthanded polypetide helices are
twisted together to form a righthanded superhelical structure.
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 proteins
•
•
•
•
Structurally complex
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)
Examples of Tertiary structure…
sperm whale myoglobin
Examples of Tertiary structure…
Examples of Tertiary structure…
Examples of Tertiary structure…
Quaternary structure
• Spatial arrangement of subunits (different polypeptide
chains) within the proteins
• Subunits generally associate through non-covalent
interactions and, in some cases, disulphide bonds
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.
Model of protein folding
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.
Importance of structure:
one example of protein misfolding
• Prion diseases
– “misfolded” protein appears to be causative agent of many
rare degenerative brain diseases in mammals
Prions…
• Stanley Prusiner was awarded the 1997 Nobel Prize in
Physiology or Medicine for his work on “prions”
• Prion: name derived from proteinaceous and infectious
– current definition: proteinaceous infectious particle that lacks
nucleic acid
• Prion diseases are invariably fatal neurodegenerative diseases,
including bovine spongiform encephalopathy (BSE), scrapie of
sheep, and Creutzfeldt-Jakob disease (CJD) of humans.
Structures of prion proteins
Taken from: Prusiner, 1998. Proc Natl. Acad. Sci. USA 95:13363-13383.
Prion diseases…
• May be present as genetic, infectious, or
sporadic disorders
• All involved modification of the prion protein
(PrP)
• Prions are transmissible particles, devoid of
nucleic acid, and apparently composed
exclusively of a modified protein.
Prion diseases
• The normal cellular PrP (PrPC) is converted to
modified protein through a posttranslational
process during which it acquires a high bsheet content.
• Normal soluble form thus converted to
insoluble form.
Stained section of the
cerebral cortex from a
patient with CreutzfeldtJakob disease shows
spongiform (vacuolar)
denegeration
Collagen Diseases
• Scurvy
• Brittle bone disease
Deficiency of Protein in Human
• Growth Failure
• Kwashiorkor
• Marasmic Kwashiorkor
• Muscle wasting
Excess of Protein in Human
Stress in kidney