Controlling protein interaction

Question 1

Give examples of diseases caused by loss of control of proteins?

Answer 1

Cancer
Polycystic kidney disease
Haemophilia

Question 2

What are the symptoms of haemophilia?

Answer 2

Spontaneous bleeding
Prolonged bleeding from cuts
Nosebleeds with no known cause
Tightness in your joints
Internal bleeding

Question 3

What is a linear enzyme pathway?

Answer 3

One enzyme promotes a response in one other enzyme

Question 4

What are amplifying enzyme pathways?

Answer 4

One enzyme promotes a response in two enzymes, which trigger two more each

Question 5

What things can activate or inactivate enzyme?

Answer 5

Allosteric
pH
Covalent

Question 6

What controls the amount of protein in a cell?

Answer 6

The level of transcription

This is controlled by transcription factors and promoters

Question 7

What controls the level of mRNA and protein?

Answer 7

Regulating their degradation

Question 8

How is a protein labelled for degradation?

Answer 8

Protein is ubiquitinated by ubiquotin
Then enters a proteasome
Proteasome and ubiquitin are recycled
Protein fragments released

Question 9

What is an effector?

Answer 9

A molecule whose binding induces a conformational change that either activates or inhibits

Question 10

What is the smallest effector?

Answer 10

H+

Question 11

What is the largest effector?

Answer 11

Another protein

Question 12

What are competitive inhibitors?

Answer 12

Effectors that bind to the effective site

Question 13

What are allosteric effectors?

Answer 13

Effectors that bind to regions away from the active site but can still regulate conformation and activity

Question 14

What may allosteric proteins show?

Answer 14

Multiple ligand binding sites

Demonstrate co-operative ligand binding

Question 15

What is allosteric regulation?

Answer 15

Production inhibition/ feedback control
Multiple and enzymes are involved
The final end product is an inhibitor of the first enzymes activity

Question 16

What does product inhibition ensure?

Answer 16

That the activity of an enzyme is reduced when there is sufficient product of the pathway

Question 17

How is protein kinase A activated by cAMP?

Answer 17

Inactive PKA is bound to inactive catalytic subunits
cAMP binds to the regulatory subunits of PKA
The catalytic subunits are activated and released

Question 18

What does control by ligand-dependent dissociation of regulatory subunits allow for?

Answer 18

Wide range of outcomes

Question 19

What expresses cooperative binding?

Answer 19

Haemoglobin

Question 20

What are some of the functions of interaction domains?

Answer 20

Localisation on other molecules
Recruiting other proteins
Creation of signal hubs
Autoinhibition

Question 21

What is localisation?

Answer 21

Regulating proteins that don’t have a single function by regulating where they are in the cell

Question 22

What are protein switches?

Answer 22

Not all protein activities run continuously and are turned on or off
Most protein switches are enzymes that catalyse the hydrolysis of a nucleotide triphosphate

Question 23

Give examples of protein switches

Answer 23

GTPase

ATPase

Question 24

How do protein switches cause cancer?

Answer 24

K-Ras GTPase is mutated in ~40 colorectal cancers

Mutated so it cannot be turned off

Question 25

Describe protein modifications

Answer 25

50% of proteins are covalently modified
Modifications change protein localisation, activity, interaction, degradation
Reversible or irreversible

Question 26

Give examples of protein modification

Answer 26

Phosphorylation
Glycosylation
Ubiquitination
Sumoylation
Disulfide bonds
Acetylation
Lipidation
Methylation
Hydroxylation

Question 27

What is phosphorylation?

Answer 27

Covalent addition of a phosphate to an amino acid side chain
Phosphate derived from adenosine triphosphate
Adds a double negative charge which has dramatic effects on protein conformation

Question 28

What catalyses phosphorylation?

Answer 28

Kinases

Question 29

What reverses phosphorylation?

Answer 29

Phosphatases

Question 30

What are cyclin-dependent kinases?

Answer 30

Essential regulators of cell division