2. STRUCTURAL ORGANIZATION

3. Protein Structure
Built from 20 kinds of amino acids

4. STRUCTURAL ORGANIZATION
Each Protein has a three dimensional structure.
Majority of proteins are compact.
Highly convoluted molecules.
Proteins are folded polypeptides.
There are four levels of organization.
Convoluted means twisted or coiled

5. What is a Protein Fold?
Compact, folding arrangement of the polypeptide chain
Chain folds to optimise packing of the hydrophobic residues in the interior core of the protein

6. Four Levels of Protein Structure
1. Primary structure
Amino acids joined by peptide bonds form a linear polypeptide chain
2. Secondary structure
Polypeptide chains form sheets and coils
3. Tertiary structure
Sheets and coils pack into functional domains
4. Quaternary structure
__2 or more separate polypeptide chains combine to form 3D structure.

7. Different Levels of Protein Structure
NH2
Lysine
Histidin
Valine
Arginine
Alanine
COOH

8. PRIMARY STRUCTURE
The numbers of amino acids vary (e.g. insulin 51, lysozyme 129, haemoglobin 574, gamma globulin 1250)
Polar amino acids (hydrophillic) tend to be placed on the outside of the protein.
Non-polar (hydrophobic) amino acids tend to be placed on the inside of the protein

9. PRIMARY STRUCTURE The number of possible sequences is infinite .
An average protein has 300 amino acids.
At each position there could be one of 20 different amino acids = possible combinations
© 2007 Paul Billiet ODWS

10. Levels of Protein Structure: Primary

11. SECONDARY STRUCTURE
Polypeptide chains tend to twist or coil upon themselves.
Held together by H bonds.
Each amino acid is spatially related to its neighbour in the same way, is the Secondary Structure of Protein.
It may take any form either α-Helix or β pleated sheet
Pleated means folded on it self
SPATIAL---CLOSELY

12. STRUCTURE OF α-HELIX
The folding of the polypeptide chain occurs using weak hydrogen bonds

13. Properties of alpha helix
It is clockwise , spiral
First -NH and last C=O groups at the ends of helices do not participate in H-bond
Ends of helices are polar, and almost always at surfaces of proteins
Always right- handed because proteins have L-amino acids.
More stable form.
Easily stretchable.

14. STRUCTURE OF β-PLEATED SHEETS
This produces the beta pleating
The length of the helix or pleat is determined by the number of amino acids .

15. PROPERTIES OF β-PLEATED SHEETS
The peptide strands may run in the same direction (Parallel strands)or may be
( anti-parallel strands).
They are in elastic because the H bonds are at right angles to the direction of stretching.
Collagen is an example.

16. Levels of Protein Structure:Secondary

17. Beyond Secondary Structure
Supersecondary structure (motifs): small, discrete, commonly observed aggregates of secondary structures
b sheet
helix-loop-helix
bab
Domains: independent units of structure
b barrel
four-helix bundle

18. Common motifs

19. Common folds

20. TERTIARY STRUCTURE
The folding of the polypeptide and refolded on itself, to give rise to a definite three dimensional confirmation which makes it globular and rigid structure.

21. TERTIARY STRUCTURE
This folding is held together by strong covalent bonds (e.g. cysteine-cysteine disulphide bridge)
H bonding
Attraction between COOH group and NH group
Ester linkage between COOH group and a OH group

22. Stabilizing Cross-Links
Cross linkages can be between 2 parts of a protein or between 2 subunits
Disulfide bonds (S-S) form between adjacent -SH groups on the amino acid cysteine

23. Formation of Binding Site
The binding site forms when amino acids from within the protein come together in the folding
The remaining sequences may play a role in regulating the protein’s activity

24. Levels of Protein Structure:Tertiary

25. QUATERNARY STRUCTURE
The quaternary protein structure involves the clustering of several individual peptide or protein chains into a final specific shape. Bonding interactions including hydrogen bonding, salt bridges, and disulfide bonds hold the various chains into a particular geometry.

26. Quaternary Structure
Refers to the organization of subunits in a protein with multiple subunits, may be identical or different.Subunits have a defined arrangement
held together by weak, noncovalent interactions (hydrophobic, H bonds,ionic bonds) .There are two major categories of proteins with quaternary structure - fibrous and globular.

27. Fibrous proteins such as the keratins in wool and hair.
QUATERNARY STRUCTURE
Fibrous proteins such as the keratins in wool and hair.
Examples of Globular proteins include insulin and hemoglobin.

28. Structural and functional advantages of quaternary structure
Stability: reduction of surface to volume ratio
Bringing catalytic sites together
There are a number of advantages in forming oligomers:
size without loss of stability
modular construction – one gene – big protein
complex catalytic sites in enzymes
regulation – will return to this briefly later 28 40

29. Levels of Protein structure: Quartenary

30. Normal Hemoglobin Structure

31. Why is Protein Structure So Important?
Protein structure dictates function.
Sometimes a mutation in DNA results in an amino acid substitution that alters a protein’s structure and compromises its function
Example: Hemoglobin-S leading to sickle-cell anemia

32. abnormal beta chain in HbS molecules. Instead
VALINE
HISTIDINE
LEUCINE
THREONINE
PROLINE
VALINE
GLUTAMATE
One amino acid substitution results in the
abnormal beta chain in HbS molecules. Instead
of glutamate, valine was added at the sixth
position of the polypeptide chain.
sickle cell
Normally rounded red blood cells are converted into sickle shapes.
normal cell

33. Biology/Chemistry of Protein Structure
Primary Secondary Tertiary Quaternary
Assembly
Folding
Packing
Interaction
S T R U C T U R E
P R O C E S S

34. Protein Structure Primary structure (Amino acid sequence) ↓
Secondary structure （α-helix, β-sheet）
Tertiary structure （Three-dimensional structure formed by assembly of secondary structures）
Quaternary structure （Structure formed by many polypeptide chains） 34

36. Denatured Proteins
If a protein unfolds and loses its three- dimensional shape (denatures), it also loses its function
Caused by shifts in pH or temperature, or exposure to detergent or salts
Disrupts hydrogen bonds and other molecular interactions responsible for protein’s shape

37. Applications of Denaturation
Denaturation of protein occurs when
an egg is cooked