Proteinopathies

Question 1

Describe the formation of an alpha helix?

Answer 1

Hydrogen bonds between carbonyl oxygen atoms of each peptide with the amid hydrogen atom from an amino acid four positions towards the c terminus

Question 2

Describe the formation of a beta pleated sheet?

Answer 2

hydrogen bonds between strands of polypeptide which can be parallel or antiparallel

Question 3

What type fo bond is a key component of tertiary protein structure?

Answer 3

disulphide bond

Question 4

There is normally a balance between protein synthesis and degradation. T/F?

Answer 4

True

Question 5

The is considerable variation in the time taken for a protein to adopt a final conformation. T/F?

Answer 5

True

Question 6

the more crowded the cellular environment, the more there is an increased tendency for proteins to aggregate. T/F?

Answer 6

True

Question 7

What is a molecular chaperone?

Answer 7

Any protein which interacts with, stabilises or helps another protein to acquire its functionally active conformation without being present in its final structure

Question 8

Chaperones selectively bind to short stretched of hydrophilic amino acids. T/F?

Answer 8

False - it is hydrophobic amino acids

Question 9

What are the functions of molecular chaperone proteins?

Answer 9

Help with de novo folding and refolding

assist oligomeric assembly, protein trafficking and proteolytic degradation

Question 10

Describe the process of the quality control process which regulates. protein folding

Answer 10

Three sugar groups are attached to a newly synthesised protein, two of these are cleaved by glucosidase one and two
This allows binding of a chaperone protein which allows time for the protein to fold properly
Glucosidase two then cleaves off the other sugar and the chaperone
Glucyltransferase detects any hydrophobic proteins present on the surface of the protein which indicate incorrect protein folding and add a sugar group to send the protein back to the chaperone binding stage
if the protein is continuously misfiled it is labelled by ubiquitin for destruction by the proteasome

Question 11

What percentage of newly synthesised proteins are misfiled?

Answer 11

30%

Question 12

The alpha subunits of a protesome are proteolytic and the beta subunits are structural. T/F?

Answer 12

False - the opposite is true

Question 13

Describe how ubiquitin causes proteasome degradation of a protein?

Answer 13

Ubiquitin tags a protein for proteasome destruction, ubiquitin is recognised by CAP and removed from the protein. The protein is then unfolded and threaded through into the proteasome

Question 14

What is a proteinopathy?

Answer 14

accumulations of misfolded proteins resulting in aggregates, thereby gaining toxic activity or losing normal function

Question 15

What is a transmissible spongiform encephalopathy?

Answer 15

A rare, progressive and fatal neurodegenerative disorder characterised by a loss of motor coordination and behavioural changes which can be inherited, sporadic or acquired

Question 16

Describe how prion infection causes spongiform degeneration?

Answer 16

It induces the normal form of the protein PrPc to adopt an abnormal secondary structure (with increased beta pleated sheets) PrPSc which causes the formation of amyloid prion rods, amyloid plaques and spongiform degeneration