Protein Structure and Diseases of Misfolding

Question 1

What is the primary structure of proteins?

Answer 1

Sequence of amino acids and a description of the covalent bonds linking the amino acid residues

Question 2

What are peptide bonds?

Answer 2

Amide linkages between amino acids formed by a condensation reaction

Question 3

What are the oligopeptides?

Answer 3

Dipeptide
Tripeptide
Tetrapeptide

Question 4

Why is primary structure so important?

Answer 4

Proteins with similar functions have similar amino acid sequences

Question 5

What is the secondary structure of a protein?

Answer 5

Local conformation of part of the polypeptide

Question 6

What are the two types of secondary structure that are particularly stable and occur widely?

Answer 6

Alpha helix
Beta sheet

Question 7

What is the tertiary structure of proteins?

Answer 7

Overall 3D arrangement of all the atoms in a single polypeptide chain

Question 8

What is the quaternary structure of proteins?

Answer 8

Overall 3D arrangement of 2 or more polypeptide subunits - refers to the organisation of protein subunits

Question 9

What suffix is used when discussing quaternary structure?

Answer 9

-meric

Question 10

What are molecular chaperones?

Answer 10

They interact with partially folded or misfolded proteins and help facilitate proper folding

Question 11

What is denaturation?

Answer 11

The loss of 3D structure that results in a loss of function

Question 12

How does Alzheimer’s disease occur?

Answer 12

Formation of spontaneously aggregated protein with results in the accumulation of plaques of insoluble beta-amyloid in the brain
An incorrect form of the tau protein causes neurofibrillary tangles which result from disruption of the cytoskeleton in affected neurons

Question 13

How does Creutzfeldt-Jakob Disease occur?

Answer 13

Misfolded PrP acts as a template for converting normal protein to a pathogenic beta-sheet form

Question 14

How does Osteogenesis Imperfecta occur?

Answer 14

Perturbed collagen structure, which is due to a single amino change of G to an amino acid with a larger R group
Perturbs the collagen helical structure

Question 15

Explain how Cystic Fibrosis occurs.

Answer 15

Defects in a chloride channel (CFTR)
Normally localises to the cell surface where it controls the passage of Cl-, making it important for the correct make up of body fluid such as mucus in lungs
Patients usually have breathing difficulties and lung infections due to abnormal mucus
Condition manifests itself when a patient has two copies of the CFTR gene which causes misfolding of the CFTR protein and its blockage in the ER

Question 16

Explain how hereditary haemochromatosis occurs.

Answer 16

Individual cannot control their levels of iron, leading over a period of decades to vital organ damage due to the build up of iron free radicals
HFe gene is the most commonly affected with a C282Y mutation
This mutation perturbs the transport of the Hfe protein to the cell surface - a protein critical for iron metabolism
If not properly localised, the levels of iron in the body build up and leads to vital organ damage
Symptoms range from chronic fatigue, joint pain, impotence, diabetes, heart disease