Cmb Week 4

Front 1

Advantages to eukaryotic compartmentalization (3)

Back 1

Create environment for optimal enzymatic activity
Localize reactions, improve efficiency by concentrating substrates/enzymes
Increase surface to area ratio

Front 2

Evolutionary origin of membrane bound compartments (2)

Back 2

Invagination to form nucleus, ER
Endosymbiosis to form mitochondria, chloroplasts

Front 3

Where do proteins from the ER go? (5)

Back 3

plasma membrane, ER, lysosomes, endosomes, secretory vesicles

Front 4

Where do proteins from free ribosomes go?

Back 4

cytosol, nucleus, peroxisomes, chloroplasts, mitochondria

Front 5

What does scramblase do?

Back 5

Lipids are synthesized on external leaflet of ER, scramblases balance lipids

Front 6

Describe the signaling and production of a protein destined for the inner ER

Back 6

1. Protein synthesis begins
2. Start Signal sequence emerges from ribosome (N-terminal sequence, 1 basic AA, 6-20 ydrophobics)
3. SRP binds, stops translation, brings ribosome to SRP receptor
4. SRP receptor binds to Sec61translocator
5. SRP and receptor dissociates, leaving ribosome bound to sec61 translocator
6. Protein exuded into lumen
7. Signal peptidase cleaves signal sequence
8. Protein released into lumen

Front 7

Describe how a protein with terminal start sequence is inserted into the ER membrane. Where is the N terminus? C terminus?

Back 7

7. Protein extrudes a "stop sequence," hydrophobic sequence of 19-25 hydrophobic AA into sec61 translocator
8. Polypeptide chain exits laterally from translocator
9. Synthesis of protein continues on cytosol side, N terminus is within ER lumen
N terminus is inside, C terminus outside

Front 8

Describe how a protein with internal non-cleavable start transfer sequence is inserted into the ER membrane. Where is the N terminus? C terminus?

Back 8

N or C terminus can be inside
1. Start transfer sequence within polypeptide chain
2. "loop" enters ER via sec61 translator
3. Amide or carboxyl end is threaded through sec61
4. Escapes laterally into lipid bilayer

Front 9

Describe how a multiple pass protein is inserted into the ER membrane. What determines start and stop transfer sequences?

Back 9

○ Alternate start and stop transfer sequences
○ n-terminal start sequences get cleaved
1. Sec61 binds to n-terminal start sequence OR internal non-cleavable start sequence
2. Polypeptide begins to thread through
3. Reaches a stop sequence (next stretch of 19-25 hydrophobic AAs)
4. Exits laterally

Front 10

What do chaperones bind to?

Back 10

○ Hydrophobic patches
○ Incompletely trimmed sugars
○ Oxidized cysteine residues

Front 11

How does an N-linked carbohydrate signal for correct protein folding?

Back 11

1. Initial: 2 terminal glucoses removed
2. Binds calnexin (chaperone)
3. Released, 3rd glucose removed
4. If its good, released from ER
5. If no good, add glucose, goes back to calnexin
6. Meanwhile, enzyme is slowly removing mannose residues (slower than glycocylation)
7. Ultimately removal of mannose residues leads to degradation

Front 12

What is ERAD

Back 12

ER associated protein degradation

Front 13

Where do proteins exiting golgi go? (3)

Back 13

○ Signal mediated diversion to lysosomes
○ Constitutive secretory pathway
○ Signal mediated diversion to secretory vesicles for regulated secretion (released on cue)