The document discusses the classification and organization of protein structures including primary, secondary, tertiary, and quaternary levels, detailing the characteristics and functions of different types of proteins. It explains the role of peptide bonds, protein folding, and chaperones in maintaining protein structure, along with diseases resulting from misfolded proteins such as prion disease and Alzheimer's. Additionally, the document outlines methods for studying protein structures, including amino acid sequencing and structural determination techniques.

1. Classification of protein
ORGANISATION OF
PROTEIN STRUCTURE

2. After the end of the class we
shall be able to-
• Classify proteins
• Tell Structural level of proteins
• Understand Bonds involved in organising protein structure
• Explain How proteins are folded
• Enumerate diseases due to misfolding of proteins.
• Describe prion disease.

3. MCQ
• 1) which of the following is not a feature of peptide
bond?
a) rigid b) partial double bond c) planar d) cis configuration
2) Which of the following is not a secondary structure of
protein?
a) Beta sheet b) beta turn c) beta helix d) beta turn
3) Which of the following is an important chaperon?
a) Hsp 50 b) titin c) hsp 70 d) Synuclein

4. • 4) which structure of protein is retained after
denaturation?
a) Primary b tertiary c) secondary d) quaternary
5) Which of the following is due to misfolding of
protein?
a) Parkinson‘s disease b) scleroderma c) renal tubular
acidosis d) myocardial infarction

5. CLASSIFICATION OF PROTEINS

6. Based on shape
1) Globular proteins : Polypeptide chains
fold into spherical or globular shape. E.g –
Albumin, Globulin etc.
2) Fibrous proteins : Polypeptide chain
arranged in long strands or sheets. E.g –
Keratin, Myosin etc

7. Based on functions

Catalytic :- Enzymes.
 Structural :- Collagen.
 Contractile :- Myosin, Actin.
 Transport :- Haemoglobin.
 Hormones :- Insulin, Growth hormone.
 Genetic :- Histones.
 Protective :- Immunoglobulins.

8. Based on composition
• Simple protein e.g Albumin, Globulin
• Conjugated protein – Contain covalently bound non protein part
which can not be separated without loss of protein activity.
• Lipoprotein e.g LDL
• Glycoprotein e.g
• Nucleoprotein e.g Histone
• Metalloprotein e.g Hemoglobin

9. Structure of proteins
• Primary structure
• Secondary structure
• Tertiary structure
• Quaternary structure
Proteins have different level of organization -

11. PRIMARY STRUCTURE OF PROTEINS

12. The primary structure of the protein refers to
sequence of amino acids .

13. Peptide bond

14. Formation of peptide bond
 Formed by a condensation reaction of alpha
carboxylic group of one amino acid and alpha amino
group of another amino acid with removal of one
molecule of water .

16. Characteristics of peptide bonds
• Partial double bond .
• The distance is 1.32A* which is in between single bond
( 1.49 A*) and double bond (1.27A *).
• Rigid and planar - Free rotation is not possible
• Rotation is possible on either side of peptide bond i.e
around C-C alpha and C alpha –N bond.
• The angle of rotation is called Ramachandran angle

20. To cond ..
• Peptide bonds are resistant to heating and
high concentrations of urea.
• Prolonged exposure to a strong acid or
base at elevated temperatures is required
to break these bonds non enzymatically.

21. Secondary structure
• Folding of short ( 3 – 30 residue) contiguous
segment of polypeptide into geometric ordered unit.
• Due to non covalent bonding.
• Types –
1) α-helix
2) β-pleated sheet

24. .
Alpha-Helix
 Most common stable confirmation of a polypeptide
chain .
 Right handed spiral structure .
The side chains of amino acids extending outwards .
α-helix is stabilized by extensive hydrogen bonding .

28. To contd.
• Average amino acid per turn 3.6 residue.
• Pitch is 0.54 nm.
• Example - Hemoglobin and Myoglobin.
• Helix breaker – Proline, glycin

30. 2 .beta pleated sheets
The second recognizable regular secondary structure in
proteins.
Distance between the two adjacent amino acid residue
(3.5 A).
It is stabilized by hydrogen bond between amide
hydrogens and carbonyl oxygen groups of adjacent
segments of beta sheet.
The backbone of the polypeptide chain is highly

32. Types of beta sheet
Antiparallel Beta sheet –
N-terminal and C-terminal ends of the adjacent β-
strands are in opposite direction.
 Parallel Beta sheet - All the N terminal ends of the β-
strands are in same direction.

34. A β turn that links two
segments of Antiparallel β
sheet.
Type I and type II turns
are most common .
Proline and glycine
often are present in β turns
Proline causes a kink in
polypeptide chain .
 Glycine with smallest side
chain frequently found
β turns

35. loops
• Loops are regions that contain residues beyond the
minimum number necessary to connect adjacent regions of
secondary structure.
• Irregular in conformation.
• For many enzymes, the loops that bridge domains
responsible for binding substrates often contain
aminoacyl residues that participate in catalysis .

36. Contd …
• Helix-loop helix motifs provide the oligonucleotide-
binding portion of many DNA binding proteins such as
repressors and transcription factors.
• Loops lack structural regularity.
• Conformation stabilized through hydrogen bonding, salt
bridges, and hydrophobic interactions with other portions
of the protein

37. Ramachandran plot
Graphical representation of combination of phi
and psi angles to study which protein
conformation will be allowed or disallowed.
•The deeper the blue, the more
thermodynamically favorable the phi–psi
combination.
•Phi–psi angles corresponding to specific types
of secondary structures are labeled

39. Super secondary structure
• Intermediate in scale between secondary and tertiary
structures.
• Specific combination of alpha helix and beta helix sheets.
• Structural motifs such as the helix-loop-helix motif or the
E-F hands of calmodulin.

40. Tertiary structure of protein
• The term “tertiary structure” refers to the entire three-
dimensional conformation of a polypeptide.
• The amino acid residues placed far apart in primary or
secondary structure interact to form tertiary structure.
• Produced and maintained by Hydrogen bonds,
Hydrophobic bonds, electrostatic bonds and Van der
Waals interaction.

42. domains
• Domains are the fundamental functional and three-
dimensional structural units of polypeptides.
• Polypeptide chains that are greater than 200 amino acids
in length consist of two or more domains.
• The core of a domain is built from combinations of super
secondary structural elements (motifs).
• Each domain has the characteristics of a small, compact
globular protein . These are connected with relatively
flexible areas of protein .

43. Protein folding
• Anfinsen’s law – The information of folding is contained in the primary structure.
• Interactions between the side chains of amino acids determine how a long
polypeptide chain folds into the intricate three-dimensional shape of the functional
protein.
• Occurs within the cell in seconds to minutes
• Involves non random, ordered pathways.
• Molten globule
• All proteins do not fold spontaneously. They require other accessory proteins called
chaperons.

44. Role of chaperones in protein
folding
• The chaperones, also known as “heat shock proteins” (Hsp), interact
with a polypeptide at various stages during the folding process.
• Some chaperones bind hydrophobic regions of an extended
polypeptide and keep the protein unfolded until its synthesis is
completed (e.g - Hsp70).
• The partially folded protein enters a cage, binds the central cavity
through hydrophobic interactions, folds, and is released (for
example, mitochondrial Hsp60)

45. Prion disease
• Neurodegenarative diseases caused by misfolded proteins.
• Also called spongiform encephalopathy.
• Mad cow disease, Scrapie in animals and Kuru Creutzfeldt-Jakob disease in human.
• Causative agent is prion protein (PrP sc).
• Normal PrP C containing alfa helical structure is converted to PrP sc containing beta
sheets.
• May manifest as genetic, infectious or sporadic disease.

47. Diseases due to misfolding of
proteins
• Amyloidosis ( systemic)
• Alzheimer’s disease
• Parkinson’s disease
• Huntington’s disease
• Type 2 Diabetes mellitus

48. QUATERNARY STRUCTURE OF
PROTEINS
• Quaternary structure defines the polypeptide composition of a
protein and, for an oligomeric protein, the spatial relationships
between its subunits.
• Subunits are held together primarily by noncovalent interactions
- Hydrogen bonds
- Ionic bonds
- Hydrophobic interactions

49. To cont...
Depending on the number of polypeptide chain , protein is
termed as –
 Monomeric proteins consist of a single polypeptide chain.
 Dimeric proteins contain two polypeptide chains. Ex – creatine kinase
 Homodimers contain two copies of the same polypeptide chain, while
in a Heterodimer the polypeptides differ.
 Oligomeric proteins contain more than two polypeptide chains.

50. Denaturation of proteins
• Disruption of three dimemsional folding of protein with loss
of biological activity.
• All level of structures are destroyed except the Primary Structure.
• Denatured proteins quickly precipitate in aqueous solution.
• Heat, strong acid or bases, ionic detergents, heavy metal ions etc
are denaturing agents.
• Reversal of denaturation is called renaturation clasically was
demonstrated in Ribonuclease A.

51. Study of protein structure
• Determination of amino acid sequence by using Edman’s
or Sanger’s reagent.
• Three dimensional structures are determined by X-ray
crystallography or by NMR Spectroscopy.