Protein structure and functional types

Question 1

How are Peptide bonds made from the condensation of amino acids? (2)

Answer 1

1. If we have a chain of amino acids, we can take an amino acid and do a condensation reaction making a peptide bond resulting in a primary sequence which can be designated with certain letters.
2. Within these proteins, the peptides are linked together forming a chain resulting in the primary structure.

Question 2

What is the N-terminus and C-terminus (nomenclature) (4)

Answer 2

1. N-terminus and C-terminus is used when naming peptide chains
2. When naming, we name from N-terminus to C-terminus
3. The N-terminus is the first amino acid in a protein chain.It has a free amine group (-NH₂).
4. The C-terminus is the last amino acid in a protein chain. It has a free carboxyl group (-COOH).

Question 3

What is the N and C-terminus for the peptide: lys-val-phe-gly-arg-cys

Answer 3

1. N-terminus = lys
2. C-terminus = cys

Question 4

What is the N and C-terminus for the peptide: asp-arg-val-tyr-ile-his-pro-phe

Answer 4

1. C-terminus = phe
2. N-terminus = asp

Question 5

What are the primary, secondary, tertiary, quarternary structures (4)

Answer 5

1. Primary structure - the sequence
2. Secondary structure - interactions between chains (e.g. helix)
3. Tertiary structure - bonds within chains (e.g. disulphate bonds, etc…)
4. Quaternary structure - whole proteins interacting with each other (e.g. in haemoglobin when oxygen binds then information is transmitted between subunits)

Question 6

What are secondary structure features (3)

Answer 6

1. alpha helix - held together by hydrogen bonding, there can also be prolines and some charged residues
2. Random coil
3. Beta pleated sheets - anti-parallel structures - held together by hydrogen bonds - N → C direction in one, then C → N in the other.

Question 7

Which beta-sheet is more stable and why

Answer 7

Antiparallel beta sheets are more stable because of their more optimal hydrogen bonding structure

Question 8

What makes peptides fold into secondary structures, e.g. helices, beta-sheets (amyloids in Alzheimer’s) – H-bonds, etc (2)

Answer 8

1. If there are hydrophobic areas (hydrophobic residues) this is a force (hydrophobic effect) which forces the protein to start folding adjacent to one another.
2. This leaves the hydrophilic areas on the surface, which can be exposed to solvent.

Question 9

What makes secondary structures fold into correct tertiary conformations – salt bridges etc, hydrophobics, disulphide bridges, e.g. insulin (5)

Answer 9

1. The final stable shape (tertiary structure) adopted by a protein is usually the most energetically favourable.
2. The protein often tests a variety of conformations before reaching its final form, which is unique and compact.
3. Folded proteins are stabilised by thousands of interactions between amino acids
4. Chemical forces between a protein and its environment contribute to protein shape and stability.
5. In terms of bonding, covalent bonds and Non-covalent bonds (e.g. ionic, salt bridges, hydrogen bonds or van der Waals interactions)

Question 10

How does tertiary protein structure differ in the cytoplasm and in the cell membrane (2)

Answer 10

1. Proteins in the cytoplasm have hydrophilic side chains on their surfaces and hydrophobic elements tucked inside
2. Proteins in the cell membrane have some hydrophobic chemical groups on their surface when exposed to membrane lipids.

Question 11

How do quarternary structures form and their interactions with DNA (coiled-coil motifs) & protein-protein interactions. (4)

Answer 11

To form a quaternary structure, proteins can:

1. associate with one another = monomer
2. interact with one another (protein-protein interactions) = homodimer (same protein) / heterodimer (different proteins) / trimer (3 identical proteins)
3. interact with genetic material (e.g. multiprotein complex bound to DNA)
4. communication between subunits - cooperativity (e.g. oxygen binding to haemoglobin)

Question 12

Difference between fibrous and globular proteins (5)

Answer 12

Globular:
1. roughly ball-shapes (sphero-proteins)
2. usually water soluble - polar groups on the surface

(e.g. blood albumin, haemoglobin and most enzymes)

Fibrous:
1. Long and thin shapes (scleroprotein)
2. many fitted together in simple repeat units
3. usually insoluble in water

(e.g. collagen, keratin (structural proteins))

Question 13

Difference between simple and complex proteins (2)

Answer 13

Simple:
1. Only a polymer of amino acids that folds into a protein

Complex:
1. A polymer of amino acids with other molecules attached (e.g. phosphates, sugars, lipids)

Question 14

Functional types of proteins: structural (e.g. collagen) (3)

Answer 14

1. Fibrous proteins that forms long polypeptide chains and forms a trimetric helix.
2. Most abundant protein in animals, forming most connective tissues (e.g. ligaments, cartiliage, blood vessels, bone and skin).
3. Used in reconstructive surgery and cosmetic surgery

Question 15

Functional types of proteins: transmembrane (signalling) (2)

Answer 15

These proteins are in the plasma membrane and help the cell interact with its environment.

1. Hydrophobic amino acids where the proteins contact lipids in the membrane bilayer
2. Hydrophilic amino acids on the surfaces that extend to the water-based cytoplasm. These parts of membrane proteins that extend beyond the lipid bilayer into extracellular environment are frequently modified by the addition of sugar molecules

Question 16

Functional types of proteins: transport (lipoproteins) (4)

Answer 16

1. Important in normal function in the vascular system.
2. Because fats (e.g. cholesterol) don’t dissolve in water lipoproteins carry them where they need to go.
3. LDL (Low-density lipoprotein) transports fats to cells (aka “bad cholesterol”) - high levels associated with the risk of heart disease
4. HDL (High-density lipoprotein) transports cholesterol away from arteries to the liker (aka “good cholesterol”)

Question 17

Functional types of proteins: nucleoproteins (2)

Answer 17

1. These are proteins associated with nucleic acids (DNA, RNA) as a way of packaging DNA (e.g. nucleosomes which are globular positively charged proteins (histones) with DNA wrapped around it).
2. Post-translationally modified by lysine acetylation, which neutralises the positive charge, reducing the electrostatic attraction between the histone and the negatively charged DNA backbone. This makes DNA accessible for transcription.

Question 18

Functional types of proteins: phosphoproteins (2)

Answer 18

1. Addition of a negatively charged phosphate group can lead to major changes in protein structure, leading to the well-characterised role of phosphorylation in
   controlling protein function.
2. Usually involved in cell signalling

Question 19

Functional types of proteins: enzymes (3)

Answer 19

1. Enzymes are proteins that aid the biochemical reactions in a cell
2. Enzymes make a biochemical reaction more likely to proceed by lowering the activation energy of the reaction, thereby making these reactions proceed much faster than without a catalyst.
3. Enzymes are highly specific to their substrates with the exception of (e.g. drug metabolism)

Question 20

Regulation of protein function by posttranslational modification, e.g. phosphorylation and change in the structure (4)

Answer 20

1. Proteins are sometimes altered after translation and folding are complete.
2. In such cases, transferase enzymes add small modifier groups, such as phosphates or carboxyl groups, to the protein.
3. These covalent modifications often shift protein conformation and act as molecular switches that turn the activity of a protein on or off.
4. Many post-translational modifications are reversible, although different enzymes catalyse the reverse reactions.

Question 21

Protein misfolding can cause disease–proteinopathies, e.g. Alzheimer’s disease (2)

Answer 21

1. Amyloid fibrils are ordered protein aggregates that have an extensive beta sheet structure due to intermolecular hydrogen bonds and have an overall similar appearance to the proteins they are derived from - different functions.
2. Will become a major problem in the UK (& worldwide) in the next few years - pharmacists will need to be aware of this.

Question 22

Proteins can be used as medicines - biologics. (2)

Answer 22

1. Biologics (proteins e.g. replacement proteins or antibodies) used to treat many diseases.
2. Interfere with cell signalling/growth: alert immune cells to destroy pathogens or tune down the immune system