1. Chapter 11. Protein Structure and Function These are biopolymers that are constructed from a limited set of amino acids. They are the most plentiful organic substances in the cell. About half of the dry mass of a cell is composed of proteins. They serve a wide range of functions.

2. Protein function EnzymesEnzymesbiological catalysts. Immuno-Immuno- antibodies of immune system. globulins TransportTransportmove materials around - hemoglobin for O 2. RegulatoryRegulatoryhormones, control of metabolism. StructuralStructuralcoverings and support - skin, tendons, hair, bone. MovementMovementmuscle, cilia, flagella.

3. Amino acids All proteins are composed of amino acids. Twenty common amino acids. All are  -amino acids. Except for proline, primary amino- group is attached to the  carbon - the carbon just after the acid group. H | R-C-COOH R-C-COOH | NH 2 NH 2 General Structure  carbon

4. Amino acids Because both acid and base groups are present, an amino acid can form a +/- ion. H H | | R-C-COOH R-C-COO - | | NH 2 NH 3 + zwitterionThe position of the equilibrium is based on pH and the type of amino acid. Called a zwitterion.

5. Some amino acid examples H 3 C H 3 C H \ \ | HC HC-C-COO - / / | H 3 C H 3 C + NH 3 valine H | CH 3 - CH 3 -C-COO - | + NH 3 alanine H | CH 3 -S-CH 2 -CH 2 CH 3 -S-CH 2 -CH 2 -C-COO - | + NH 3 methionine NH H | CH 2 CH 2 -C-COO - | + NH 3 tryptophan

6. Some amino acid examples H | HO-CH 2 HO-CH 2 -C-COO - | + NH 3 serine H | H H-C-COO - | + NH 3 glycine O O H | | | | | H 2 N-C-CH 2 H 2 N-C-CH 2 -C-COO - | + NH 3 asparagine O O H | | | | | O-C-CH 2 -CH 2 - O-C-CH 2 -CH 2 -C-COO - | + NH 3 glutamic acid

7. Abbreviations glycine Gly G alanine Ala A valine Val V leucine Leu L isoleucine Ile I methionine Met M phenylalanine Phe F tryptophan Trp W proline Pro P

8. Groups of Amino Acids Hydrophobic Polar, neutral Negatively charged positively charged

9. Primary protein structure Proteins are polymers made up of amino acids. Peptide bondPeptide bond - how the amino acids are linked together to make a protein. H | H 2 NCCOOH | | R R + H H | | H 2 NCCOOH | | R’ R’ H O H O | || | || H 2 N - C - C - | | R R H H | | N - C - COOH | | | | H R’ + H 2 O

10. Four levels of protein structure Primary structurePrimary structure The sequence of amino acids in a protein. Secondary structureSecondary structure Way that chains of amino acids are coiled or folded - (  -helix,  -sheet, random coil). Tertiary structureTertiary structure Way  -helix,  -sheet, random coils fold and coil. Quaternary structureQuaternary structure Way that two or more peptide chains pack together.

11. All proteins have the same covalent backbone. Part of a protein. Primary structure H O H O | || | || H 2 N - C - C | | R R H H | | NH - C - COOH | | R’’’ R’’’ H O H O | || | || - NH - C - C - | | R’ R’ H O H O | || | || - NH - C - C - | | R’’ R’’

12. Secondary structure Long chains of amino acids commonly fold or curl into a regular repeating structure. Structure is a result of hydrogen bonding between amino acids within the protein. Common secondary structures are:  - helix  - pleated sheet Secondary structure adds new properties to a protein like strength, flexibility,...

13.  -helix One common type of secondary structure. Properties of an  -helix include strength and low solubility in water. Originally proposed by Pauling and Corey in 1951.

14.  -helix

15. Every amide hydrogen and carbonyl oxygen is involved in a hydrogen bond.

16. Collagen Family of related proteins. About one third of all protein in humans. Structural proteinStructural protein Provides strength to bones, tendon, skin, blood vessels. tropocollagenForms triple helix - tropocollagen.

17. Tropocollagen

18.  -Pleated sheets Another secondary structure for protein. Held together by hydrogen bonding between adjacent sheets of protein. C|RC|R R|CR|C R|CR|C R|CR|C R|CR|C C|RC|R C|RC|R C|RC|R C|RC|R C|RC|R N|HN|H N|HN|H N|HN|H O || C O || C O || C O || C || O C || O C || O C || O H|NH|N H|NH|N H|NH|N H|NH|N N|HN|H

19.  -Pleated sheets Silk fibroinSilk fibroin - main protein of silk is an example of a  pleated sheet structure. Composed primarily of glycine and alanine. Stack like corrugated cardboard for extra strength.

20. Beta sheet

21. Tertiary structure of proteins Fibrous proteinsFibrous proteins insoluble in water form used by connective tissues silk, collagen,  -keratins Globular proteinsGlobular proteins soluble in water form used by cell proteins 3-D structure - tertiary

22. Tertiary structure of proteins Results from interaction of side chains. The protein folds into a tertiary structure. Possible side chain interactions:Possible side chain interactions: Similar solubilities Ionic attractions Electrostatic attraction between  + and  - sidechains Covalent bonding

23. Tertiary structure of proteins - S - S - Salt bridge Sulfide crosslink Hydrogen bonding Hydrophobic interaction -COO - H 3 N + - -O \ H -O \ H

24. Quaternary structure of proteins Many proteins are not single peptide strands. They are combinations of several proteins - aggregate of smaller globular proteins. Conjugated proteinConjugated protein - incorporate another type of group that performs a specific function. prosthetic groupprosthetic group

25. Quaternary structure of proteins Aggregate structure This example shows four different proteins and two prosthetic groups.

26. Hemoglobin and myoglobin HemoglobinHemoglobin oxygen transport protein of red blood cells. MyoglobinMyoglobin oxygen storage protein of skeletal muscles. As with the cytochrome example, both proteins use heme groups. It acts as the binding site for molecular oxygen.

27. Heme myoglobinmyoglobin 1 heme group hemoglobinhemoglobin 4 heme groups

28. Myoglobin Heme

29. Hemoglobin 4 heme 2  chains 2  chains

30. Oxygen Transport

31. Example - cytochrome C 550 Aggregate of proteins and other structures. Heme structure Contains Fe 2+ Used in metabolism.

32. Sickle cell anemia Defective gene results in production of mutant hemoglobin. Still transports oxygen but results in deformed blood cells - elongated, sickle shaped. Difficult to pass through capillaries. Causes organ damage, reduced circulation. Affects 0.4 % of African-American.

33. Comparison of normal and sickle cell hemoglobin NormalSickle

34. Summary of protein structure primarysecondary tertiaryquaternary H O H O | || | || H 2 N - C - C | | R R H H | | N - C - COOH | | | | H R’’ H O H O | || | || - NH - C - C - | | R’ R’

35. Denaturation of Proteins The loss of secondary, tertiary, and quaternary structures 1) pH extremes. 2). Heat - 3). Mechanical Agitation (foaming) 4). Detergents 5). Organic Solvents 6). Inorganic Salts -