1. AH Biology: Unit 1 Protein Structure 1

2. Think What are the functions of protein in a cell?
Why is protein structure important?
Why do organisms usually live within a narrow range of temperature and pH?
If eukaryotic cells are identical in structure relative to their cellular components why do organisms look different?
How can a gecko stick to Perspex?
How do multicellular organisms stay together?
Think about these questions and answer them as you study this section on protein structure.

3. The structure of proteins LOs
The amino acid sequence determines protein structure.
Primary sequence- amino acids are linked by peptide bonds into polypeptide chains.
Secondary structure- hydrogen bonds form alpha helices, beta sheets (parallel or anti-parallel) or turns.
R groups can be polar, negatively charged, positively charged or hydrophobic.

4. The structure of proteins Los
Tertiary structure- caused by interactions between R groups such as ionic bonds, hydrogen bonds, van der waals interactions, disulphide bridges.
Prosthetic groups can give proteins an extra function (i.e. haem in haemoglobin).
Quaternary structure- several polypeptide subunits join.
Temperature and pH can affect interactions of the R groups.

5. Four levels of protein structure
5. Protein Structure Summary
Using A3 paper, present this information as a summary. Use the Scholar guide and your LOs for guidance.
Split into 4 groups
On an A1 show me board:
2. What do you already know about the level of protein structure assigned to you?
3. What can you add?
4. Share your information with the class
Use the image as a brief starting point to outline main differences of four levels of structure only. Following slides will provide details.
Primary
structure
Secondary structure
Tertiary
Quaternary structure

6. Primary protein structure
Proteins are polymers of amino acid monomers. A monomer is the simplest unit of a polymer. There are 20 amino acids in total.
The primary sequence of a protein is the order in which the amino acids are synthesised by translation into the polypeptide.

7. Zwitterion: amino acids
Is a base as the N terminus is free to accept hydrogen ions from solution.
Is an acid as the C terminus is free to donate hydrogen ions.
The charge on an amino acid and therefore a protein is pH dependent.

8. Primary protein structure
Interactive amino acids
Peptide bonding
Primary structure

9. Peptide bond formation
A peptide bond is formed between the carboxylic acid (–COOH) terminal of one amino acid and the amine (–NH2) terminal of another.
This is a condensation reaction as water is produced.
As a result, all proteins have a carboxyl terminus (end) and an amine terminus.

10. Secondary protein structure
Hydrogen bonding along the backbone of the protein strand results in regions of secondary structure called alpha-helices, parallel or antiparallel beta-sheets or turns. These cause the protein to have a three-dimensional shape as the linear polypeptide backbone begins to fold.
Alpha-helices and beta-sheets

11. Alpha-helix
Hydrogen bonding between the N–H and C=O groups of every 3.5 amino acid residues in the polypeptide backbone.

12. Beta-sheet Antiparallel Parallel
Hydrogen bonding between the N–H and C=O groups of the amino acid residues in the polypeptide backbone.

13. Beta-sheet

14. Amino acids and R groups
R groups are the residues or side chains of the 20 amino acids, which have different functional groups.
Positively charged, basic
Negatively charged, acidic
Polar
Hydrophobic, non-polar
Uncharged polar
These functional groups give the protein its function as they interact with each other and with other structures associated with the protein.

15. Amino acids and R groups
R group properties test

16. Acidic Amino Acids Generally have a COOH on the R group
This allows them to donate a proton (H+) to another atom.
They become –vely charged and strongly hydrophilic.
There are only two amino acids with negatively charged (i.e. acidic) R groups - these are Aspartate (Aspartic acid) and Glutamate (Glutamic acid). 
Aspartic Acid
Glutamic Acid

17. Basic Amino Acids Generally have a NH2 on the R group.
This allows them to accept a proton (H+) and become +vely charged.
They become strongly hydrophilic.
There are 3 basic amino acids: Lysine, arginine and histidine
Lysine

18. Polar Amino Acids
They all have oxygen or nitrogen or sulfur on their R side chain.
They are hydrophilic as they form weak hydrogen bonds with water molecules.
There are six polar amino acids including serine and cysteine.
Serine
Cysteine

19. Non-Polar Amino Acids
The R group does not contain OH, COOH, NH2 or SH.
They do not become charged.
They are hydrophobic.
Includes glycine and phenylalanine.
Glycine
Phenylalanine

20. Tertiary structure
The polypeptide folds further into a tertiary structure.
This conformation (shape) is caused by interactions between the R groups.
Hydrophobic interactions
Ionic bonds
Hydrogen bonds
Van der Waals interactions
Disulfide bridges.
Prosthetic groups (non-protein parts) give proteins added function.

21. Ionic bonds
Charge dependent attraction occurring between oppositely charged polar R groups, eg between the amino acids arginine and aspartic acid.
pH affects ionic bonding and results in denaturation of the protein at extremes of pH as the H+ and OH– ions in solution interact with the charge across the ionic bond.

22. Hydrogen bonds
Hydrogen bonding is a weak polar interaction that occurs when an electropositive hydrogen atom is shared between two electronegative atoms.
Hydrogen bonding is charge dependent.
pH affects hydrogen bonding and results in denaturation of the protein at extremes of pH as the H+ and OH– ions in solution interact with the charge across the hydrogen bond.

23. Ionic and hydrogen bonds

24. Van der Waals interactions
Weak intermolecular force between adjacent atoms.
Geckos and Van der Waals forces.

25. Disulfide bridges
Covalent bonds that form between adjacent cysteine amino acids.
These can occur within a single polypeptide (tertiary structure) or between adjacent polypeptides (subunits, quaternary structure).

26. Prosthetic groups
These are additional non-protein structures that are associated with the protein molecule and give it its final functionality.
Examples:
chlorophyll (magnesium centre), responsible for light capture in photosynthesis
haem (iron centre), found in red blood cells in haemoglobin and responsible for oxygen carriage.

27. Chlorophyll

28. Haem

29. Tertiary structure
Tertiary structure review
Human pancreatic lipase

30. Quaternary structure
Quaternary structure exists in proteins with several connected polypeptide subunits.
These subunits are held together by all of the interactions listed in the tertiary structure.
Quaternary structure review
Immunoglobulins
Keratin

31. Haemoglobin: four subunits and four haem groups

32. Effects of temperature and pH on protein shape
Any factor that changes the interactions of the R groups will change the shape of the protein.
Temperature and pH can influence the interactions of the R groups.
If the protein has lost its shape (and so its functionality) it has been denatured.
Increasing temperature will first disrupt (melt) weaker bonds and then finally stronger covalent bonds.
pH can shift the acid/base characters of the R groups on particular amino acids and so change the ionic interactions in the chain.
Denaturation review

33. Effects of temperature and pH

34. The structure of proteins Key Concepts
The _________ _______sequence determines protein structure.
Primary sequence- amino acids are linked by _________ bonds into __________ chains.
Secondary structure- _________ bonds form ______ _______, beta sheets (_______ or ___-_______) or turns.
R groups can be _______, ________ charged, _______ _________or _________.

35. The structure of proteins Key Concepts
The amino acid sequence determines protein structure.
Primary sequence- amino acids are linked by peptide bonds into polypeptide chains.
Secondary structure- hydrogen bonds form alpha helices, beta sheets (parallel or anti-parallel) or turns.
R groups can be polar, negatively charged, positively charged or hydrophobic.

36. The structure of proteins Key Concepts
Tertiary structure- caused by interactions between __ ______such as _______ bonds, hydrogen bonds, ____ ____ _____interactions, _________ bridges.
_________ groups can give proteins an extra function (i.e. ______ in haemoglobin).
Quaternary structure- several _________ subunits join.
_________ and ____ can affect interactions of the R groups.

37. The structure of proteins Key Concepts
Tertiary structure- caused by interactions between R groups such as ionic bonds, hydrogen bonds, van der waals interactions, disulphide bridges.
Prosthetic groups can give proteins an extra function (i.e. haem in haemoglobin).
Quaternary structure- several polypeptide subunits join.
Temperature and pH can affect interactions of the R groups.

38. Hydrophobic and hydrophilic interactions LOs
The R groups at the surface of a protein determine its location within a cell.
Hydrophilic (water loving) R groups will predominate at the surface of a soluble protein found in the cytoplasm.
In these proteins, hydrophobic (water hating) R groups may cluster at the centre to form a globular structure.
Regions of hydrophobic R groups allow strong hydrophobic interactions that hold integral proteins within the phospholipid bilayer. Some integral proteins are transmembrane, for example channels, transporters and receptors.
Peripheral proteins have fewer hydrophobic R groups interacting with the phospholipids.

39. Hydrophobic interactions
The R groups at the surface of a protein determine its location within a cell.
Hydrophilic (water loving) R groups will predominate at the surface of a soluble protein found in the cytoplasm.
In these proteins, hydrophobic (water hating) R groups may cluster at the centre to form a globular structure.
 Hydrophobic sections of proteins are classically found embedded in the phospholipid bilayer of a cell, while the hydrophilic polar parts are free to interact with the extracellular and intracellular solutions.

40. Hydrophobic and hydrophilic interactions
The R groups at the surface of a protein determine its location within a cell.
Protein trafficking animation of Golgi apparatus.
Protein transport animation and the enzymes involved.
The Golgi apparatus is responsible for preparing the protein for its final destination within the cell.
The proteins could be destined for several locations, for example:
intracellular environment: cytoskeleton production of tubulin, actin and myosin
organelles such as mitochondria and chloroplasts
the cell membrane: transmembrane proteins, extrinsic and intrinsic
extracellular excretion: extracellular digestion via trypsin, liapse etc.

41. The fluid mosaic model of membrane structure
Another introductory slide – the details will be expanded upon in the following slides.
The fluid mosaic structure of the cell is composed of phospholipids, cholesterol and proteins.
The fluid mosaic model looks like a Roman mosaic of phospholipids and embedded proteins.
The proteins are free to move within the cell membrane to where they are required as the demands of the cell change.

42. The fluid mosaic model of membrane structure
Phospholipid
Cholesterol
Glycolipid
Sugar
Integral transmembrane protein
Integral glycoprotein
Integral protein anchored by a phospholipid
Perihperal glycoprotein
Mitochondria animation for membrane proteins. Discuss hydrophobic and hydrophillic interactions, and ATP synthase.

43. The fluid mosaic model of membrane structure
Regions of hydrophobic R groups allow strong hydrophobic interactions that hold integral proteins, those embedded in the membrane, within the phospholipid bilayer as they are free to interact with the hydrophobic tails of the phospholipids.
Some integral proteins are transmembrane and cross the phospholipid bilayer, for example:
channel proteins: facilitated diffusion and active transport
transporters: sodium potassium pump
receptors: G-proteins.

44. Hydrophobic and Hydrophilic Interactions -Key Concepts
The ____ groups at the surface of a protein determine its _______ within a cell.
__________ (water loving) R groups will predominate at the ______ of a soluble protein found in the cytoplasm.
In these proteins, _______ (water hating) R groups may cluster at the centre to form a _______ structure.
Regions of hydrophobic R groups allow strong hydrophobic interactions that hold _______ proteins within the _________ bilayer. Some integral proteins are transmembrane, for example _______, ________ and _________.
_________ proteins have fewer hydrophobic R groups interacting with the __________.

45. Hydrophobic and Hydrophilic Interactions -Key Concepts
The R groups at the surface of a protein determine its location within a cell.
Hydrophilic (water loving) R groups will predominate at the surface of a soluble protein found in the cytoplasm.
In these proteins, hydrophobic (water hating) R groups may cluster at the centre to form a globular structure.
Regions of hydrophobic R groups allow strong hydrophobic interactions that hold integral proteins within the phospholipid bilayer. Some integral proteins are transmembrane, for example channels, transporters and receptors.
Peripheral proteins have fewer hydrophobic R groups interacting with the phospholipids.

46. Think What are the functions of protein in a cell?
Why is protein structure important?
Why do organisms usually live within a narrow range of temperature and pH?
If eukaryotic cells are identical in structure relative to their cellular components why do organisms look different?
How can a gecko stick to Perspex?
How do multicellular organisms stay together?
Think about these questions again and answer them as part of a discussion in class based on what you have learned in this section.

47. Key Area 1.2 Protein structure
Past Paper Practice
Advanced Higher
Key Area 1.2
Protein structure

48. The diagram below represents the structure of the amino acid alanine.
In the diagram, the R group has the composition
A —H
B —NH2
C —CH3
D —COOH.

49. The diagram below represents the structure of the amino acid alanine.
In the diagram, the R group has the composition
A —H
B —NH2
C —CH3
D —COOH.

50. An enzyme-controlled reaction is taking place in optimum conditions in the presence of a large surplus of substrate.
Conditions can be altered by
increasing the temperature
adding a positive modulator
increasing enzyme concentration
increasing substrate concentration
Product yield would be increased by
A 1 and 2
B 2 and 3
C 2 and 4
D 3 and 4

51. An enzyme-controlled reaction is taking place in optimum conditions in the presence of a large surplus of substrate.
Conditions can be altered by
increasing the temperature
adding a positive modulator
increasing enzyme concentration
increasing substrate concentration
Product yield would be increased by
A 1 and 2
B 2 and 3
C 2 and 4
D 3 and 4

54. Which of the proteins shown are integral membrane proteins?.
The diagram below shows the arrangement of four proteins (R, S, T and V) and the phospholipid bilayer of a cell membrane
Which of the proteins shown are integral membrane proteins?
A S only
B R only
C S, R and T only
D S, R, T and V

55. Which of the proteins shown are integral membrane proteins?.
The diagram below shows the arrangement of four proteins (R, S, T and V) and the phospholipid bilayer of a cell membrane
Which of the proteins shown are integral membrane proteins?
A S only
B R only
C S, R and T only
D S, R, T and V

56. Give details of the structure of proteins including primary, secondary, tertiary and quaternary levels. (10 marks)

57. Primary structure of a protein is the sequence of amino acids in the polypeptide chain.
Amino acids are joined together by peptide bonds.
Secondary structure of a protein is stabilised by hydrogen bonds.
α-helix and β-sheet are two types of secondary structure.
α-helix is a spiral with the R groups sticking outwards.
β-sheet has parts of the chain running alongside each other forming a sheet.
The R groups sit above and below the sheet.
. β-sheet can be anti-parallel or parallel.

58. 9. Turns are a third type of secondary structure.
10.Tertiary structure refers to the final 3D structure of the protein.
11. Folding at this level is stabilised by many different interactions between the R groups of the amino acids.
12.Any two from: hydrophobic regions, ionic bonds, hydrogen bonds, van der Waals interactions, disulfide bridges.
13. Tertiary structure of a protein may include prosthetic (non-protein) parts.
14.For example, haem in haemoglobin.
15. Quaternary structure exists in proteins with several connected polypeptide subunits.