BIOL340 Proteostasis (3.1)

Question 1

What is a protein?

Answer 1

Linear chain of amino acids encoded by a DNA blueprint

Question 2

What is the proteome?

Answer 2

Genomes encode all proteins that form the proteome

Question 3

What state are proteins functional in?

Answer 3

Folded, Native Scape

Question 4

What are the levels of protein structure?

Answer 4

Primary, Secondary, Tertiary, Quaternary

Question 5

What is a domain?

Answer 5

Spatially-disctinct modules of a protein, functioning in semi-independence

Question 6

How are domains grouped?

Answer 6

Into families based on structural similarities

Question 7

What level of structure determines 3D structure?

Answer 7

Primary Structure

Question 8

What is Levinthal’s Paradox?

Answer 8

Proteins have an infinite number of conformations, but folding only takes seconds/minutes

Question 9

What state are folded proteins in?

Answer 9

The most thermodynamically favourable, having the lowest energy.

Question 10

What are the two main folding pathways?

Answer 10

Hydrophobic Collapse and Nucleation of Folded Domains

Question 11

Describe hydrophobic collapse

Answer 11

Hydrophobic residues find each other in the protein, causing collapse

Question 12

Describe nucleation of folded domains

Answer 12

Local interactions form secondary structure, with one domain folding leading to further folding

Question 13

Where are the hydrophobic residues?

Answer 13

Internalised

Question 14

What is the major concept of proteostasis?

Answer 14

Turn over of proteins, and the maintenance of proteins

Question 15

When does protein misfolding occur?

Answer 15

In the disordered state

Question 16

What forms an amporphous precipitate?

Answer 16

Amorphous aggregation pathway; Fast, disordered aggregates

Question 17

What forms a fibril

Answer 17

amyloid fibril pathway; slow and highly ordered

Question 18

Are aggregates visible in solution?

Answer 18

Yes

Question 19

What is needed for a diagnosis of Alzheimers?

Answer 19

Protein aggregate formation in the brain

Question 20

What are some common aggregation related diseases?

Answer 20

Alzheimers, parkinsons, systemic amyloidosis,

Question 21

What are the areas of protoestasis control?

Answer 21

Extracellular proteostasis, synthesis and folding, aggregation, HSPs, UPS, ERAD, Autophagy

Question 22

What are the fates for non-native proteins

Answer 22

Rescue by chaperones
Degradation by proteases
Aggregation

Question 23

Describe the general features of chaperones

Answer 23

recognise and bind non-native proteins, assiting in folding and assembly, as well as prevenitng protein aggregation

Question 24

Describe general fetarues of holdases

Answer 24

Bind hydrophobic regions, protecting from inappropriate interactions; Hold but do not refold; ATP independent

Question 25

Describe general features of foldases

Answer 25

Faciliatate correct folding by regulated binding and release; ATP-dependent; prevent inappropriate interactions

Question 26

Describe foldase chaperone (Hsp70) action

Answer 26

Polypeptide emerges from ribosome; Hsp70 chaperones bind to elongating polypeptide; Hsp70 shields from inappropriate interactions; Release of polypeptide for proper folding

Question 27

Describe foldase chaperone Hsp60 action

Answer 27

non-native protein binds to hydrophobic region inside GroEL; GroES attaches; GroEL cavity increases, protein refolding occurs; ATP hydrolysis and GroES is released; Folded protein released

Question 28

What are the 2 ways of protein degradation?

Answer 28

proteasome and lysosome

Question 29

What does the proteasome do

Answer 29

Chops protein into singular amino acids

Question 30

How does the proteasome work

Answer 30

non-native protein recognised by ubiquitin ligases; poly-ubiquitinated protein binds to cap of proteasome; ubiquitin is removed and protein is fed into chamber; amino acids cut and released

Question 31

What motif is recognised in chaperone mediated autophagy?

Answer 31

KFERQ, recognised under stress

Question 32

What does recognition of KFERQ do

Answer 32

direction to lysosomes

Question 33

What is the purpose of the aggregosome

Answer 33

Moves aggregated proteins to one point to have a central point for machinery to act

Question 34

What occurs in uncontrolled aggregation

Answer 34

Formation of an inclusion body