Structure of Proteins

Question 1

What are the possible functions of proteins ? Provide an example for each

Answer 1

1. Providing structure (collagen in bone, skin, tendon)
2. Transport molecules (haemoglobin which carries 02 through Iron at center of heme group in each of the 4 subunits AND LDL and HDL receptors which coordinate uptake of LDL and HDL into cell)
3. Defence (Antibodies)
4. Biological catalysts (enzymes, such as lysozymes)
5. Regulation of Genes (lac repressor)

Question 2

What is the function of LDL ?

Answer 2

Transporting cholesterol molecules between cells via circulatory system

Question 3

How are LDL receptors related to atherosclerosis and hypercholesterolaemia ?

Answer 3

Atherosclerosis might arise as a result of poor regulation of cholesterol transport.
Hypercholesterolaemia may have mutation in LDL receptor gene affecting how it is made or affecting intake by cells

Question 4

What is the structure of antibodies ?

Answer 4

2 identical heavy chains and 2 identival light chains covalently linked by disulphide bonds.

Question 5

What is the function of lysozymes ?

Answer 5

Catalyse cutting of polysaccharide chains.

Question 6

What is the role of lac repressor ? What is its mechanism ?

Answer 6

Helps control gene expression.
Controls production of proteins metabolising lactose in bacteria so binds to DNA and prevents expression of the gene in the absence of lactose.

Question 7

Are proteins linear ?

Answer 7

YES (AAs joined by peptide bonds)

Question 8

What is primary structure ?

Answer 8

Sequence of AAs

Question 9

What are hydrophilic (acidic, basic, and polar uncharged), hydrophobic, and special ones ?

Answer 9

Hydrophillic
Acidic: Eglutamate Daspartate
Basic: Klycine Rarginine Histidine
Uncharged: Serine Naparagine Tthreonine Qglutamine

Hydrophobic:
Valine Alanine Leucine Isoleucine Methionine Fphenylalanine Ytyrosine Wtryptophan

Special ones:
Glycine Cysteine Proline

Question 10

What are the special features of proline, cysteine and glycine ?

Answer 10

Glycine is the smallest one
Cysteine forms covalent disulphide bonds
Proline creates kink in protein chain

Question 11

What is the Henderson Hasselback equation ?

Answer 11

Equation used to calculate pH of a reaction pH=pKa + log([A-]/[HA])

Question 12

What is an acid ?

Answer 12

A molecule which tends to release an H+ ion

Question 13

What is a base ?

Answer 13

A molecule which tend to readily combine with a hydrogen ion

Question 14

How do we determine the pKa of an acid ?

Answer 14

It is the pH at which half the molecules are dissassociated

Question 15

What is the biological significance of the the acid/base properties of AA side chains ?

Answer 15

• Overall charge of AA and hence proteins varies with pH
• Local environment may influence pKa which is especially important because close to the pKa, small changes in pH can cause significant changes in charge carried.
• pH one unit lower than pKa, only 10% dissociated so mostly acid form of the AA
• pH one unit higher than pKa 90% dissociated so mostly basic form of the AA

Question 16

Give an example of a protein for which acid/base properties does matter.

Answer 16

LDL receptor. Reduction of pH in endosomes (to around 5) causes change in conformation of LDL receptor due to presence of histidine reside within the protein (pKa 6.5) –> LDL can no longer bind and is released to lysosome

Patients with hypercholesterolaemia often have mutations in the histidine resides of the LDL receptor

Question 17

How do two AAs combine ?

Answer 17

Through peptide bonds, the formation of which requires condensation.

Question 18

What are the constraints imposed by peptide bonds ?

Answer 18

• NO ROTATION ALLOWED (so only rotation around alpha carbon)
• Bulky R groups positioned on either side of the backbone (one up one down)
• conformation of folded polypeptide chain determined by one pair of angles for each AA residue.

Question 19

What is the secondary structure of proteins ? What different types are there ?

Answer 19

Initial folding pattern of linear polypeptide, stabilise by H-bonds.
Alpha helix
Beta plated sheet
Bend/loop

Question 20

What are the main characteristics of alpha helices ?

Answer 20

• Right handed
• 3.6 AA residues per turn
• Helix stabilised by H bonds between Amino and Carboxyl groups of every 4th AA

Question 21

What are the main characteristics of beta helices ?

Answer 21

• Beta strands (extended stretches of 5 or more AAs) organised next to each other
• H-bonding pattern depends on whether parallel (adjacent strands oriented in same direction N to C) or antiparallel
• B sheets may be mixes of parallel and anti-parallel

Question 22

What are the main characteristics of Bend/loops ?

Answer 22

• Polypeptide chains folding upon themselves
• Usually 4 AAs per turn
• Proline residues frequently found in bends/loops