Macromolecules 3: Proteins

1. Macromolecules 3: Proteins

2. Additional Resources (1) The Tree of Life, proteins and DNA module

3. Additional Resources (2) Protein structure and conformation links • Molecular Workbench DNA and protein module • Summary of protein confirmation • Protein movie

4. 7.5.4: State 4 functions of proteins, giving a named example of each • Structural support (Fibrous proteins) Silk: cocoons and webs Keratin: hair, horns, skin, nails, wool, beaks Collagen: tendons and ligaments PDB 101

5. 2.Enzyme Function (Globular soluble) Amylase Catalase Pepsin Trypsin DNA helicase DNA synthase Etcetc etc…

6. 3. Protein hormones Globular soluble • Insulin • ACTH • Vasopressin • Somatostatin • Prolactin • Growth hormone

7. 4. Transport proteins (Globular, soluble) Haemoglobin, myoglobin: transport of essential substances (oxygen, carbon dioxide) Myoglobin was the first protein to be thoroughly described

8. 5. Energy storage: soluble Ovalbumin, Casein (milk protein), storage proteins in plant seeds

9. 6. Movement proteins Actin and myosin form muscle fibres Animation of actin/myosin

10. 7. Receptor proteins (also pumps, channel proteins) • Adrenergic receptors • G-protein receptors • Cannabinoid receptors • Opioid receptors • Aquaporin channels • Na/potassium pump proteins

11. 8. Immune function:Antibodies (Immunoglobulins) Globular soluble proteins: IgG, gA, IgM,

12. Proteins • > 50% of the dry mass of a cell is protein Proteins are used for: • Structural support • Energy storage • Transport of other substances • Signalling from one part of the organism to another • Movement • Defence against foreign substance • Enzymes • Humans have tens of thousands of different proteins • Most structurally sophisticated molecule, due to unique 3D shape or conformation

13. Protein Functions

14. Amino Acid (Monomers) • Amino acid structure: NH2- C - COOH • Amino acids differ due to the R (functional) group • The structure of the R-group determines the chemical properties of the amino acid

15. Amino Acids link together to form polypeptides • 2 Amino Acids form a covalent bond, called a PEPTIDE BOND, through a condensation reaction to form a dipeptide • Multiple amino acids can bond to each other one at a time, forming a long chain called a POLYPEPTIDE

16. Peptide Bonds – link amino acids

18. 20 Amino Acids are used in cells

20. 7.5.3: Explain the significance of polar and non-polar amino acids

21. Hydrophilic Amino Acids Polar (but uncharged)amino acids are hydrophilic & can form H-bonds • Serine • Threonine • Glutamine • Asparagine • Tyrosine • Cysteine

22. Hydrophobic Amino Acids • Glycine • Alanine • Valine • Leucine • Isoleucine • Methionine • Phenylalanine • Tryptophan • Proline) Nonpolaramino acids are hydrophobic and are usually found in the centre of the protein. They also found in proteins which are associated with cell membranes.

23. Electrically charged Amino Acids The electrically charged amino acids have electrical properties that can change depending on the pH. • Aspartic Acid • Glutamic Acid • Lysine • Arginine • Histidine

24. Special Amino Acids Cysteine can form covalent disulfide bonds Proline has a unique structure and causes kinks in the protein chain

25. ‘Essential’ Amino Acids In humans, not all amino acids can be manufactured by the body; 10 (8 in adults) must be taken in through our diet. These are the ‘essential’ amino acids

26. 7.5.1: Explain the four levels of protein structure, indicating the significance of each level

27. Four Levels of Protein Structure/ Conformation 1. Primary- unique linear sequence in which amino acids are joined, can have dire circumstances if changed (insulin) 2. Secondary - refers to three dimensional shapes that are the result of H bonding at regular intervals, due to interactions between the amino acid backbones • alpha helix is a coiled shape • beta pleated sheet is an accordion shape 3. Tertiary Complex 3-D globular shape due to interactions between R groups of amino acids in it • Globular proteins such as enzymes are held in position by these interactions 4. Quaternary Consist of more than one polypeptide chain subunits, associated with interactions between these chains 19

28. Protein Shape Determines Function • Proteins with only primary and secondary structures are called fibrous proteins (claws, beaks, keratin, wool, collagen, ligaments, reptile scales) • Proteins with only 1,2,3 shapes are called globularproteins • If a protein is incorrectly folded, it can’t function correctly • Not understood how proteins fold themselves, seem to have molecules called chaperone proteins or chaperoninsthat assist others • A protein is denaturedwhen it loses its shape and therefore its ability to function correctly 20

29. Primary Structure • A unique sequence of amino acids in a long polypeptide chain • Involves peptide bonds between the carboxyl and amine groups • Any changes in primary structure will affect a protein’s conformation and its ability to function • Example: Sickle cell anemia CYS LYS VAL PHE GLY ARG

30. Sickle cell anaemia Sickling occurs due to a mutation of the Hb gene, associated with replacement of glutamic acid by valine

31. Secondary Structure Made by hydrogen bonds between the backbone of the amino acids (amino group and carboxyl groups) • α-helices: area with a helical or spiral shape. Held together by H bonds between every 4th amino acid • β-pleated sheets:area where 2 or more regions of the polypeptide chain lie in parallel

32. αhelixa β-pleated sheet • The bonds involved are hydrogen bonds • Large proteins will have regions containing both structures

33. Tertiary Structure: FOLDING The protein folds up since various regions on the secondary structure are attracted to each other: • Disulfide Bridges:strong covalent bonds between cysteine’s sulfhydryl (-SH) groups • Ionic Bonds:between positively and negatively charged side chains • Hydrogen Bonds:between polar side groups • Hydrophobic Interactions:non-polar side chains end up on the inside of a protein, away from water

35. Quaternary Structure Complex proteins exist as aggregations of 2 or more polypeptide subunits

36. QUATERNARY STRUCTURE E.g. immunoglobulins • The bonds involved are the same as those for tertiary structure Chain 3 Chain 2 Chain 1

37. Protein denaturation Protein denaturation refers to loss of 3 – dimensional structure (and usually also biological function) of a protein – die to changing of the bonds that maintain secondary and 3rd degree structure, even though the amino acid sequence remains unaltered Denaturation can be caused by: • Strong acids and alkalis – profound pH change • Heavy metals – may disrupt ionic bonds • Heat, radiation, UV radiation • Detergents and solvents

38. 7.5.2: Outline the difference between fibrous and globular proteins, referring to 2 examples of each

39. A review from Cornell University

40. Fibrous proteins Only have primary and secondary structures • Water insoluble • VERY tough, may also be supple or stretchy • Parallel polypeptide chains in long sheets or fibres • STRUCTURAL proteins – collagen, cartilage, tendons, blood vessel walls • CONTRACTILE proteins – actin and myosin

41. Globular proteins Have all four levels of protein structure • Water soluble • Tertiary structure critical to function • CATALYTIC (enzymes) • REGULATORY – hormones (insulin) • TRANSPORT (haemoglobin) • PROTECTIVE (immunoglobulins)