3D Structure of Proteins

Question 1

What is Amyloid (A)?

Answer 1

A small protein released as a result of proteolysis of APP

Question 2

What is the most common post translational modification mutation?

Answer 2

Phenylalanine deletion at 508 residue of CFTR gene resulting in Cystic Fibrosis

Question 3

How is misfolding induced in PrPC proteins?

Answer 3

ɒ helices misfold to form a Β sheet which then induces other PrPC proteins to misfold and aggregate

Question 4

Give an example of tertiary structure

Answer 4

The 7 transmembrane domain of the thyroid stimulating hormone receptor

Question 5

What is APP?

Answer 5

Amyloid precursor protein

• large protein that regulates synapse formation
• involved in G protein signalling

Question 6

What amino acids are usually present in beta turns?

Answer 6

Glycine or Proline

Question 7

How are beta sheets stabilised?

Answer 7

By hydrogen bonding between adjacent beta strands connected by loops in both parallel
and antiparallel arrangements

Question 8

Where does the hydrogen binding occur between amino acids?

Answer 8

Between the carbonyl and amide groups

Question 9

Explain what Prions are?

Answer 9

Misfolded Proteins (PrPSC) which characterise many fatal neuro degenerative diseases

Question 10

What does the tertiary structure of a protein consist of?

Answer 10

The combination of ɒ helices and Β sheets & turns of a single polypeptide

Question 11

How does the CFTR mutation lead to cystic fibrosis?

Answer 11

ΔF508del -> protein misfolding whilst still in the ER
Recognised by cellular machinery
Resulting in ubiquitination
Trafficked to proteosome and degraded
70% of caucasian CF patients harbour this mutation

Question 12

Why does the induction of misfolding occur in PrPC proteins?

Answer 12

The dynamic process results in a more stable aggregated structure

Question 13

Describe what is meant by a proteins Quartenary structure and give an example

Answer 13

Combination of multiple polypeptide chains e.g. Haemoglobin

Question 14

What are the consequences of post translational modification mistakes in Β-amyloid cells?

Answer 14

Β-amyloid cells aggregate
interfering with synapse formation (esp. in hippocampus)
Higher order insoluble aggregates form (cross structured)
Deposited in plaques
Damage neuronal brain cells

Question 15

What determines the properties of ɒ helices and Β sheets?

Answer 15

The arrangement of the amino acids variable side chains

- they stick out from the polypeptide surface

Question 16

What is the consequence of the presence of Prions?

Answer 16

Prions interact with normal proteins (prPC) inducing misfolding of the normal proteins
which then undergo polymerisation

Question 17

Define what CFTR is?

Answer 17

Cystic Fibrosis Transmembrane Conductance Regulator

Question 18

What happens to APP in alzheimer disease?

Answer 18

APP is proteolytically cleaved resulting in a 40 residue Β-amyloid

Question 19

Without cleavage, what is the fate of APP?

Answer 19

1. APP anchors protein in the membrane
2. Causing APP to accumulate and misfold
3. Forming Β sheets in a planar arrangement
4. Β sheets polymerise to form Amyloid fibrils

Question 20

Describe the structure of Amyloid (A) fibres

Answer 20

Stacked Β sheets with the side chains interdigitating