1. PROTEINS BY DR. MARYJANE

2. INTRODUCTION Proteins are macromolecules formed of amino acids united together by peptide bonds

3. CLASSIFICATION OF PROTEINS. Proteins are classified into 4 groups: primary, secondary, tertiary and quaternary proteins

4. STRUCTURES OF DIFFERENT CLASSIFICATION OF PROTEIN

5. PRIMARY STRUCTURE OF PROTEINS Is the sequence of amino acids in a protein Understanding the primary structure of proteins is important because many genetic diseases result in proteins with abnormal amino acid sequence which results in the impairment of normal function. If the primary structures of the normal and abnormal(mutated) proteins are known, may be used to diagnose diseases.

6. PEPTIDE BOND It is a covalent bond formed between the carboxyl group of one amino acid and the amino group of another. It is formed by removal of water. Peptide formation requires energy in the form of ATP.

8. NAMING OF THE PEPTIDE BOND By convention, the free amino end of the peptide chain (N-terminal) is written to the left and the free carboxyl end (C-terminal) to the right. All amino sequence are read from the N- to C- terminal end of the peptide.

9. glycylalanylcysteine

10. glycylglycine

11. PEPTIDES Are compounds formed of 50 or less amino acids linked together by peptide bonds. 1. dipeptide: 2 amino acids 2. tripeptide: 3 amino acids 3. oligopeptide: 3-10 amino acids 4.polypeptide: 11-50 amino acids.

12. SECONDARY STRUCTURE OF PROTEINS includes α-helix β- pleated sheet β- bends

13. α-helix It is a spiral structure,consisting of a tightly packed, coiled polypeptide backbone core with the side chain of the component amino acid extending outward to avoid interference. Stabilized by hydrogen bonds btw the peptide-bond carbonyl oxygen and amide hydrogen of a peptide linkage four residues ahead in the polypeptide Examples of proteins that contains α-helices are keratins, collagen, elastin Some A.A disrupts the helix: proline, charged A.As(glutamate, aspartate, histidine, lysine or arginine), A.As with bulky side chain(tryptophan)

15. β- PLEATED SHEETS Composed of two or more polypeptide chain held together by Hydrogen bond (inter or intrachain) Types: i) parallel β-sheets: in which the two polypeptide chains run in the same direction. ii) antiparallel β-sheets: in which the two polypeptide chains run in the opposite direction.

18. TERTIARY STRUCTURE Is the folding of a polypeptide into a 3- dimensional structurural unit called a domain E.g., globular protein myoglobin

19. Tertiary Structure Myoglobin

20. BONDS RESPONSIBLE FOR TERTIARY STRUCTURE: Hydrogen bonds Hydrophobic bonds Ionic bond Disulfide bonds

21. QUATERNARY STRUCTURE OF PROTEINS Many proteins consist of a single polypeptide chain which is called a monomeric protein or a subunit. Some consists of 2 or more polypeptide chain that may be identical or unidentical. The arrangement of these polypeptide subunits is called the quaternary structure of protein 2 subunits: called a dimer 3 subunits: called a trimer 4 subunits: called a tetramer Several subunits: called a multimeric

22. BONDS RESPONSIBLE FOR QUATERNARY STRUCTURE: Hydrogen bond Electrostatic bond Hydrophobic bond. EXAMPLES OF PROTEINS HAVING QUATERNARY XTURE: Lactate dehydrogenase enzyme (tetramer) Hemoglobin (tetramer)

23. Protein folding Interactions between the side chains of amino acids determine how a long polypeptide chain folds Protein folding occurs within the cell in seconds to minutes It’s a trial and error process. 23

24. Role of chaperones Information needed for proper protein folding is contained in the primary structure of the polypeptide Protein folds in stages during synthesis rather than waiting for the synthesis of the entire chain to be totally completed. Chaperones aka “heat shock proteins” are required for the proper folding of proteins by interacting with the polypeptide at various stages during the folding process. 24

25. 25 Protein Misfolding  Protein folding is a trial and error process that is not perfect can result in improperly folded proteins called misfolded proteins  Misfolded protein-Tagged and degraded within the cell via the ubiquitin-proteasome mechanism.  Defect in this control system-Extracellular and intracellular accumulation of misfolded proteins Age Disease  Prion Disease  Amyloidosis

26. Proteasome-Ubiquitin pathway

27.  Prion protein (PrP) has been implicated as the cause of prion disease.  Prion diseases are a family of degenerative brain disorders observed in humans and numerous other mammals known as transmissible spongiform encephalopathies.  Some (but not all) cases originate by transmission from one individual to another, however, no bacterial, viral, or parasitic agent has been identified  Propagate by transmitting mis-folded protein whose configuration have been altered  Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and mad cow disease in cattle Creutzfeldt-Jakob disease Prion Disease

28. Protein Misfolding

29. Amyloidosis – Misfolding of protein due to mutation in a particular gene producing an altered protein – Normal Amyloid precursor protein undergoing Abnormal proteolytic cleavage froming Long Fibrillar protein consisting of β-pleated sheet called Amyloids Protein Misfolding

30. Causes of Alzheimer disease – Amyloid in Alzheimer’s disease –Amyloid β(A β)- Neurotoxic – Alzheimer’s disease is also due to accum of neurofibrillary tangles. A component of the the neurofibrillary tangle is an abnormal form of a protein called tau protein – Mutations in Apolipoprotein E increases susceptibility to and decreased age of onset of late-onset Alzheimer disease – familial (genetic) : 5-10%

31. DENATURATION OF PROTEINS. Protein denaturation means unfolding and loss of secondary and tertiary structures which are not accompanied by hydrolysis of peptide Denaturation may be reversible (in rare cases) when the denaturing agent is removed, but usually irreversible. EFFECTS OF PROTEIN DENATURATION: 1. Loss of biological activity e.g., 2. denatured proteins are often insoluble. 3.denatured proteins are easily precipitated.

32. Denaturating factors: 1. heat 2. organic solvents 3. detergents 4. mechanical mixing 5. strong acids or bases 6. heavy metals 7. alkaloidal reagents 8. enzymes 9. repeated freezing and thawing 10. urea, ammonium sulfate and sodium chloride.