Chaperones

Question 1

How can proteins become functional

Answer 1

• be folded to active 3D structure
• must bind to cofactors
• must be modified by protein kinases
• join other subunits

Question 2

Describe molten globule state

Answer 2

-intermediate state in-between protein folding which happens in seconds after leaving ribosome and has alpha helixes and beta sheets

Question 3

Disadvantage of misfolded proteins

Answer 3

• waste of energy to cell

- hydrophobic regions aggregate causing disease

Question 4

2 mechanisms by which cells defend against misfolded proteins

Answer 4

1 proteasomes

2 chaperones

Question 5

What are chaperones

Answer 5

-proteins which help other nascent proteins fold properly

Question 6

What system are chaperones part of and describe briefly

Answer 6

• quality control system
• protein control system : mechanism allows cells to monitor protein synthesis and ensure they are in a stable and inert state

Question 7

Functions of chaperones

Answer 7

• rescue misfolded proteins back to normal nascent state
• prevent protein degradation : normally folded not ubiquitinated
• prevent aggregation
• prevent prion formation
• assist in translocating proteins
• assist in protein folding

Question 8

What is a client protein

Answer 8

-protein helped to fold properly by chaperones

Question 9

How do chaperones aid in protein folding

Answer 9

-they bind to aggregation prone hydrophobic region and use ATP hydrolysis to perform mechanical work on protein and ensure correct folding

Question 10

How are chaperones made, example and why and their synonym

Answer 10

• made during severe stressful conditions undergone by a cell
• eg extreme heat denatures proteins and chaperones are needed to deal with denatured proteins
• heat shock proteins

Question 11

Types of chaperones and examples

Answer 11

1 heat shock 
HSP 10 - Gro ES
HSP 60 - Gro EL
HSP 70 - DNA K
HSP 40 - DNA J

2 lectin chaperones

• calnexin
• calreticulin

3 Glucose Regulated Proteins GRP-58

4 Protein disulfide isomerase

Question 12

Function lectin chaperones

Answer 12

-function in immune system by antigen processing and presentation in MHC class 1 molecule

Question 13

Function of GRP-59

Answer 13

-assist in glycoprotein folding

Question 14

Classification of proteins based on function and describe and examples

Answer 14

1 foldases - transform misfolded back up nascent state

• assist in folding
• ATP dependent
• HSP 60

2 holdases- prevent damage to protein by providing favorable conditions

• do not fold or correct misfolded proteins
• HSP 70

3 disaggregases - prevent aggregation

• rescue aggregates proteins
• prevent prion formation
• HSP 104

Question 15

List the 3 ways in which proteins can processed

Answer 15

1 on pathway folding

2 off pathway folding

3 proteasome system

Question 16

Describe on pathway folding

Answer 16

• linear sequence goes into intermediate molten globule state
• under normal conditions globule transformed into final state

Question 17

Describe off pathway folding

Answer 17

• sometimes intermediate deviates from pathway leading to misfolding
• chaperones catalyze protein to return to normal pathway
• protein gets correctly folded

Question 18

Describe proteasome system

Answer 18

• sometimes chaperones fail you catalyse misfolded protein back to pathway
• protein ubiquitinated and degraded

Question 19

When do chaperones assist in folding and give examples

Answer 19

• co translational : HSP 70

- post translational: HSP 60

Question 20

Function of HSP 70 and its domains

Answer 20

-mediates folding of newly ( co ) synthesized proteins

1 atp binding domain - n terminal
2 substrate binding domain -inside cavity
3 c terminal - provides cavity for substrate

Question 21

ATP bound to HSP 70 forms !?

Answer 21

-open complex confirmation

Question 22

Describe how HSP 70 mediates folding

Answer 22

• HSP 40 recruits substrate to HSP 70 where It binds to cavity at aggregation prone hydrophobic region
• HSP 40 and atp bringing to HSP 70 causes hydrolysis and lid closed forming closed conformation
• protein folding commences inside cavity when lid closed
• 40 leaves and nucleotide exchange factors convert adp to atp
• open complex formed at folded protein leaves

Question 23

Function of HSP 40

Answer 23

• recruits substrate to HSP 70

- regulates atp activity

Question 24

Describe what proteins are acted upon by HSP 60 and its shape

Answer 24

-completely synthesized proteins

/barrel like

Question 25

What does HSP 60 do

Answer 25

-isolates proteins and provide favorable conditions for the protein to fold

Question 26

Describe how HSP 60 does its function

Answer 26

• captures protein along its rim
• atp binds changing its shape allowing HSP 10 cap to close barrel
• inside barrel conditions are favorable and protein folds
• 15 seconds later another atp round remove caps and weaken complex allowing protein to move out of barrel

Question 27

What are prions

Answer 27

-misfolded prion protein which wasn’t degraded

Question 28

What is PRNP

Answer 28

-gene on chromosome 20 which codes for prion protein

Question 29

What is PRPc, function and PRPsc

Answer 29

• normal prion protein present on surface on neuron cells at synapses
• misfolded prion protein

Question 30

What do misfolded prions do and their effect

Answer 30

-can transform normal proteins into prions as well

/causes proteopathy- disease caused by structurally abnormal proteins wc disturpt normal function

• causes nuerodegenerative disease
• causes kuru
• mad cow disease
• scrapie disease

Question 31

Why can misfolded prions be degraded

Answer 31

-increase In b pleats from a normal prion to misfolded allow it to resist proteasomes

Question 32

How are PRPsc formed

Answer 32

• during folding prion protein is misfolded and goes off pathway
• chaperones try to repair but fail and ubiquitinated
• proteasome fails to degraded