Metabolism L6

Front 1

What are degradation signals?

Back 1

Signals which are quickly created or inmasked to target a protein for destruction eg. through phosphorylation of protein kinase or protein dissociation.

Front 2

Give an example of an intermediary between degradation signals and degradation machinery.

Back 2

Ubiquitin. Chains of it attach to the cytosolic proteins by attaching the C-terminus of a new molecule to Lys48 of the previous one.
Monoubiquitinylation signals the degradation of integral membran proteins.

Front 3

How does proteosomal degradation work?

Back 3

Cytosolic proteins designed for degradation are polyubiquitinylated by ubiquitin ligases once their degradation signal is unmasked.

Front 4

What are the steps involved in regulated protein degradation II?

Back 4

1. For inactivation, surface receptors are ubiquitinylated
2. Monoubiquitinylation of receptors induces their endocytosis
3. Endocytosed ubiquitinylated receptors are sequestered into internal vesicles of a compartment called the multivesicular body
4. Internal vesicles and their content are degraded in the lysosome.

Front 5

How is glycogen phosphorylase regulated?

Back 5

Regulated by various metabolites including adrenaline, glucagon and insulin to either be in active (R) or inactive (T) form. Kinase mediated phosphorylation also regulates allosteric regulation;
dephosphorylised = phosphorylase b
phosphorylised = phosphorylase a

Front 6

Give an example of a second type of conformational change involved in regulation.

Back 6

Calmodulin is activated by calcium when there is an increase in calcium concentration. Calmodulin undergoes a large conformational change, activating many downstream targets.

Front 7

Give a third example of a type of conformational change involved in regulation

Back 7

GTPases change conformation when hydrolysing GTP. Two switch regions change conformation, allowing GTPase to bind and modulate specific targets in the GTP bound form.
GTPases are regulated by GEF and GAP

Front 8

What side chains can be modified by phosphorylation?

Back 8

Serine, threonine or tyrosine side chains.

Front 9

What two things can phosphorylation do?

Back 9

1. Promote/inhibit the function of a protein
2. Influence enzymatic activity, protein conformation or protein interactions

Front 10

Name two kinases central for metabolism

Back 10

mTOR
AMPK

Front 11

Give examples of AGC (protein kinase A, G C)

Back 11

PKA, Akt/PKB, PKC, PKG

Front 12

Give two examples o calmodulin activated (CaM) kinases

Back 12

CaMII
PKD (lipid activation (DAG)

Front 13

What proteins are involved in partitioning between the cytosol and the membrane?

Back 13

Phosphoinositides. These can be interconverted by kniases and phosphatases which allows the speciic co-localization of signalling components, which results in their activation

Front 14

What proteins are involved in movement between intracellular compartments?

Back 14

Transcriptional activators- shuttle between nucleus and cytosol by exposing nuclear import and export signals.

Front 15

How do metabolite transporters and receptors avoid active participation in signalling at the plasma membrane?

Back 15

Use the endpcytic pathway

Front 16

What are transient protein complexes?

Back 16

Generated for a given reaction and then dissociated to stop that reaction.
They need at least one component to change its binding properties prior to binding and revert to the inactive state to dissolve the complex.

Front 17

What is signal integration?

Back 17

When signalling from two pathways are integrated by two of their cascade components interacting and transferring the signal jointly.

Front 18

Explain signal handover in the context of G proteins

Back 18

Ga subunit of trimeric G protein is activated by GPCR. It then receives GTP which allows it to bind to adenylyl cyclase. Upon GTP hydrolysis the transient Ga-adenylyl cyclase interaction is lost.

Front 19

Give examples of protein domains which have evolved to bind to particular motifs

Back 19

SH2- binds P-Tyr
SH3- binds proline rich region
PH- binds P14, 5P2

Front 20

What are the key features of an SH2 domain?

Back 20

Amino acids around pTyr provide a specificity signature:
Shc = Leu or Val at 3rd position
Lck = Ile at 3rd position
PLC-yl = needs hydrophobic residue at 2nd position
Syp = needs specific residues up to 5 aas away from pTyr

Front 21

Give two examples of pathways in which scaffolds are used.

Back 21

Cascade for mating response and glycerol synthesis; both start with same kinase but scaffolds direct signals to different targets.

Front 22

What role do scaffolds play in protein interaction?

Back 22

1. Direct cascades to different targets
2. Bring components of signal pathway together to strengthen weak interaction and allow signal propagation