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Bioc 212 > Membrane proteins Lectures > Flashcards

Membrane proteins Lectures Flashcards

1
Q

What is the function of the secretory pathway?

A

It is a transport system between several types of organelles and the cell surface (plasma membrane)
There is synthesis of proteins and lipids at the ER
There is traffic through the golgi to the plasma membrane
and there is internalization through endosomes to degradation in lysosomes.

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2
Q

What is an example of an organelle not connected to the secretory pathway?

A

The mitochondria is not connected

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3
Q

What is Lumen?

A
  • It is the interior of secretory organelles and it is continuous with each other and the extracellular space.
  • The lumenal environment contains salts, pH, proteins, and co factors are is similar to the extracellular space (blood plasma)
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4
Q

Is lumen similar to cytosol?

A

No it is different. But cytosol is still intra-cellular fluid that is present inside cells.

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5
Q

When vesicles bud from one organelle membrane and fuse with another, do they release their contents into the cytosol?

A

No they do not release their contents

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6
Q

What are some important functions that biological membranes fulfill?

A
  • Provide enclosure to cell, and to organelles within cells
  • allow regulated transport of materials between compartments
  • provide sites within cells for biochemical reactions, photosyntehsis, oxidative phosphorylation, metabolism of biological molecules (lipids, glycans, others)
  • support contacts with the environment outside cells (cell motion, recognition of other cells, cell fusion)
  • transmssion of signals from exterior to interior of cells.
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7
Q

What are 5 properties of membranes?

A

1) Form hydrophobic barriers between aqueous compartments within the cell (cytosol and organellar lumens )

2) Flexible and can be formed into different shapes

3) selectively permeable to small hydrophobic molecules, but not to large or charged/polar molecules

4) Specialized protein complexes control the movement of impermeable molecules across membranes

5) Can store energy as concentration gradients (voltage (nerve cells), pH, potassium, sodium, calcium gradients)

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8
Q

What is meant by the Fluid Mosaic Model (membranes)?

A
  • Membranes are made of lipid molecules and membrane proteins
  • Lipids are organized into a bilayer: a sheet is polar on each side and hydrophobic in the middle
  • Hydrophobicity acts as a barrier to water-soluble molecules
  • Membrane proteins can rotate and diffuse laterally in the fluid bilayer
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9
Q

What are the major membrane lipids?

A

1) Phospholipids - in all membranes

2) Glycolipids - only at plasma membrane

3) Cholesterol

All have polar and hydrophobic sections (main characteristic)
Lipid composition determines physical properties of membrane, mobility (diffusion, rotation) and curvature, thickness.

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10
Q

What are phospholipids?

A
  • They are the most abundant lipid
  • Polar head groups
    Choline or other charged group
    Phosphate and glycerol
    Classification by head groups
    Phophatidyl- choline (PC) - ethanolamine (PE), serine (PS) are the most common
  • sphingomyelin (SM) is not glycerolipid but it is related
  • Phosphatidyl-inositol (PI) is not abundant but can be phosphorylated and act as a signalling molecule.

-The head grpup size and charge effect lipids mobility

  • 2 fatty acid tails
    Different lengths
    Saturated (no double bonds) or unstaurated (1 or more double bonds)
    Hydrocarbon chain or usually 14 to 24 carbons
    Varying number of double bonds
    Saturated tails are straighter and more flexible
    Double bonds introduce bends in the tail, reduce flexibility and overall length
    The types of tails in membrane determine its thickness and fluidity
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11
Q

Where are glycolipids found? Why are they important?

A

They are found on the outside surface of the plasma membrane.
The head groups contain different sugar groups in many combinations.
It is important for cell contact with the environment and other cells.

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12
Q

What is the structure of cholesterol? How does this affect its mobility?

A
  • Cholesterol is structurally different from other lipids
  • The steroid ring structure makes it very rigid, lateral mobility and the rotation is much lower.
  • Reduces the mobility of surrounding phospholipids, which makes the fatty acid tails more rigid.
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13
Q

Are membranes asymmetric? If so, why?

A
  • Many biological membranes are asymmetric meaning tge lipid composition on each side is different
  • This is important for its function
  • The exterior has glycolipids
  • The interior has stronger negative charge (high PS levels)
    The assymetry is not absolute, but it is actievely managed.
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14
Q

What has the higher level of cholestrol?

A

The plasma membrane

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15
Q

Where do you find the highest levels of PC and PE?

A

In the ER and mitochondria.

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16
Q

What are microdomains?

A

Microdomains are regions of a membrane that are organized laterally (sideways) in patches.

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17
Q

Where are there specialized microdomains, what are they called?

A

The plasma membrane and trans-golgi have special microdomains called lipid rafts. They are thicker than surrounding membrane and enriched in cholesterol. Lipids with longer tails cluster together in rafts. The cholecterol binding straightens lipid tails and causes a thicker membrane, they have a different protein content and biological function.

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18
Q

What is the synthesis of phospholipids?

A
  • They are synthesized on the cytosolic side of the ER membrane.
  • Fatty acids (acyls) are attached to Coenzyme A in chemically reactive states.
  • Glycerol-phosphate, head group added in sequence by enzymes.
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19
Q

Describe lipid synthesis.

A
  • Phospholipids and cholesterol are synthesized on the cytosolic side of the ER membrane.
  • There is a scramble of proteins in the ER membrane that flip lipids randomly. This is an ATP-independent function.
  • Lipids are transported through secretory pathway by vesicles.
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20
Q

How is asymmetry in the membrane maintained?

A

At the plasma membrane, flippase proteins are what maintain asymmetry. This function is ATP-dependent, directional, and lipid-specific. New lipids are brought the the plasma membrane by vesicle, and then they are flipped to the correct orientation!

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21
Q

How are lipids transported?

A

Lipids are transported by:

1) vesicles between organelles of the secretory pathway
2) by carrier proteins through the cytosol
3) through contact sites between organelles (ER and mitochondria)

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22
Q

Are soluble proteins associated with membranes?

A

Soluble proteins are not associated.

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23
Q

What does the localization of membrane proteins require?

A

Requires protein-based targeting mechanisms

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24
Q

Does the structure of membrane proteins involve added contacts with lipids?

A

Yes

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25
Q

How are integral membrane proteins tightly anchored?

A

They are tightly anchored by hydrophobic interactions with the interior of the lipid bilayer. Involves 1 or more transmembrane alpha-helices.

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26
Q

Describe Membrane Biogenesis:

A
  • Cellular membranes can only be made by expanding pre existing membranes
  • With very few exceptions, all proteins are encoded by nuclear genes and translation in the cytosol
  • After, proteins must be sorted to their correct compartment or membrane. The sorting information is carried inside the proteins themselves.
  • ER membrane is where proteins are translated, and the lumen of the ER.
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27
Q

Where are secretory proteins inserted and where do they transport to?

A
  • Secretory pathway proteins are inserted into or across the endoplasmic reticulum (ER) membrane. They are then transported to further compartments such as the Golgi, Plasma membrane, endosomes and lysosomes.
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28
Q

What is a key difference between the Rough ER and the smooth ER?

A
  • In the rough ER, there are many attached ribosomes, and there is secretory protein synthesis.
  • In the smooth ER, there are no ribosomes, and it is the site of lipid synthesis.
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29
Q

What is a targeting signal?

A
  • Sequences within a protein that specify its organelle localization, it is a ‘zip code” or a signal peptide.
  • Are often independent from the structure or biochemical function of proteins.
  • recognized by a pattern, usually not an exact sequence.
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30
Q

Can targeting signals be removed?

A

May be removed by proteolysis after targeting is complete, or form part of the native structure.

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31
Q

What are the 3 targeting steps?

A

1) Recognize a signal on a protein
2) Connect protein to the membrane
3) Translocate protein into or across the membrane

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32
Q

What exits through the ribosome exit tunnel? How does this work?

A
  • Nascent polypeptides exit the ribosome through a tunnel in the large (60s) subunit
  • The tunnel is neutral, polar, too small for tertiary folding
  • Surface around exit site provides binding sites for ER targeting mechanism
  • 30 to 40 amino acids of nascent polypeptide between peptidyl-transferase site end the exit site
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33
Q

What do secretory signal peptides direct?

A

They direct proteins to the ER for translocation into or across the membrane.
- Mostly co-translationally

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34
Q

Some secretory pathway proteins have additional targeting signals that direct them to organelles. What are two examples of these?

A

1) Often could be a polypeptide motif (a sequence pattern)

2) Sometimes it could be a post-translational modification

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35
Q

Organelles not in the secretory pathway have their own targeting signals. What are 2 organelles that follow this?

A

1) mitochondria

2) nuclei

36
Q

What is the patten of a signal peptide?

A
  • There is a hydrophobic region 8 or more residues long, with polar regions on each side
  • In many cases, signal peptides are at the N terminus. There are shorter hydrophobic regions (8-16 residues) and they are often cleaved off after translation.
37
Q

What are signal anchors?

A
  • They are signal peptides that also become transmembrane helices
  • they are not cleaved off
  • they can be in different places in the protein
  • they have longer hydrophobic regions (18-24 residues)
38
Q

What are the 3 targeting steps of a signal peptide?

A

1) Recognize a signal on a newly translated protein
A. ribosome begins translating polypeptide with a signal

  1. Connect protein to the membrane
  2. Translocate protein into or across the membrane.
    A. Energy of translation on ribosome drives polypeptide through the translocon.
39
Q

What is SRP? And what is it involved in?

A

Signal Recognition Particle (SRP) is a soluble protein that binds signal and ribosome during translation.

Involved in the first targeting step of a signal peptide.

  • Ribonucleoprotein: 6 protein subunits and 1 RNA
  • Signal sequence recognition subunit with GTPase activity
  • Translation regulatory domain at the opposit end
  • RNA strand forms flexible linker
40
Q

What is SRP-R? What is it involved in?

A

A SRP Receptor (SRP-R) is a membrane protein that binds the ribosome-SRP complex.

Involved in the second targeting step of a signal peptide.
SRP-R links ribosome to translocon pore in the ER>

41
Q

How does SRP work in terms of binding signal and ribosome during translation?

A
  1. SRP samples all nascent polypeptides that emerge from ribosomes
  2. When a signal peptide is recognized, SRP attaches tightly to both the signal and the ribosome
    A. SRP pauses translation at the ribosome and binds GTP
    (SRP attached to ribosomes in GTP-bound state)
42
Q

What is the process of SRP-R to Translocon?

A
  1. Ribosome-SRP complex binds to SRP-R on the ER (SRP-R is also a GTPase, and it is GTP-bound state when it recognizes SRP-ribosomes)
  2. Ribosome moves to the translocon and becomes tighlty bound
  3. SRP and SRP-R dissociate from the ribosome.
    Now translation resumes, and a polypeptide is translocated into lumen. The lumen polypeptide does not contact the cytosol.
    (GTP hydrolysis by both SRP and SRP-R dissociate them and recycle them)
    GTP is used like a switch.
43
Q

What is a translocon?

A

The translocon is a complex of proteins associated with the translocation of polypeptides across membranes.

44
Q

Describe the Sec61 complex. (A ER Translocon)

A
  • provides the dynamic polypeptide-conducting channel, which mediates membrane insertion of most membrane proteins of organelles involved in endo- and exocytosis and translocation of all precursors of polypeptides destined for these same organelles and most precursors
  • Has 2 parts (yellow and blue) that form both sides of the eous pore
  • Inactive pore is plugged by part of protein (violet)
  • Active pore is open but tightly sealed onto ribosome
  • Inside of pore is neutral and polar
  • 2 parts of pore open laterally to intergrate TM helices
45
Q

What is translocation?

A

A genetic change in which a piece of one chromosome breaks off and attaches to another chromosome.

46
Q

What are the 3 steps of the translocation of a Lumenal protein?

A
  1. Signal peptide tiggers the opening of the translocon
  2. Polypeptides are translocated in extended, unfolded state
    A. movement of polypeptide is driven by the energy of translation pushing it out of the ribosome.
  3. Signal peptidase often removes signal peptide during translocation.
    A. not sequence-specific but has a preferred site.
47
Q

How is the transmembrane helix integrated?

A

There is a protein with a N-terminal signal sequence and a transmembrane helix.

1) Signal peptide starts the translocation of lumenal part.

2) Transmembrane helix is recognized by translocon and integrated laterally into the membrane during translation.

3) Signal anchor is recognized as a transmembrane domain and intergrated laterally.

48
Q

What are the two types of TM proteins?

A

Type 1) N-terminus in lumen, C-terminus in cytosol

Type 2) N-terminus in cytosol, C-terminus in lumen

49
Q

What is meant by the Multi-Pass of transmembrane proteins? (TM)

A

There are combinations of signal anchor and TM helices that cause alternation orientation of multi-pass TM proteins.
The topology (TN organization) of secretory pathway proteins can often be predicted. For example, you can predict the hydrophobicity (number of TM helices), charge distribution (orientation in membrane), and other modifications such as disulfide bonds, glycosylation, phosphorylation and ubiquitinaiton.

50
Q

What is N-linked glycosylation? What is the purpose?

A

Purpose:
regulates maturation of proteins through the secretory pathway.
Helps stabilize the native state
Protect against proteases
Function in the cell surface signalling

Process: the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom (the amide nitrogen of an asparagine (Asn) residue of a protein)

51
Q

What is a characteristic about N-linked glycosylaiton on the Asn side chain in context of Asn-X-Ser/Thr motif?

A
  • The same glycan is always attached to the ER
  • Mostly mannose, with 3 glucose
52
Q

What are the 4 steps of the glycosylation process?

A
  1. Oligosaccharides are synthesized attached to a specialized lipid in the ER
  2. OST attaches glycan during translocation
  3. State of glycan is used as a signal in ER quality control of folding
  4. Glycan is modifided in Golgi after exit from ER
53
Q

Where are misfolded secretory proteins degraded? How?

A

They are degraded at the ER. This can be done by the ubiquitin-proteasome system. This is the only pathway for transport of secretory proteins back to the cytosol.

Another form is degradation at lysosomes at the end of the pathway. Digestion by proteases inside lysosome.

54
Q

What are some characteristics of the ER chaperone system?

A

Involved:
BiP (HSP70)
- ERdj proteins (DNAJ co-chaperones)
- NEF co-chaperones

  • GRP94 (HSP90) - no co-chaperones

Calnexin and calreticulin
UGGT (UDP-glucose:glycoprotein glycotransferase)
glucosidases, mannosidases, lectins (glycan binding)
Degradation takes place on cytosolic proteasomes
Folding is necessary to exit ER to secretory pathway

55
Q

What is the purpose of Substrate-binding DNAJ (ERdj3)?

A

Assist in folding

56
Q

What is Sec63?

A

Specialized TM DNAJ that recruits BiP to translocation polypeptides. Does not bind substrate directly.

57
Q

Is the ER lumen an oxidizing environment?

A

Yes

58
Q

What does spontaneous disulfide formation favour?

A

Favours inefficient and/or incorrect folding

59
Q

What is disulfide formation catalyzed by?

A

By the enzyme thioredoxins. There are two reactive Cys residues that are close together and can oxidize substrate.

PDI and ERp57 help with process!

60
Q

What is PDI?

A

Protein disulfide isomerase (PDI) is a folding assistant in the endoplasmic reticulum (ER) of eukaryotic cells.

PDI has multiple roles, acting as a chaperone, a binding partner of other proteins, and a hormone reservoir as well as a disulfide isomerase in the formation of disulfide bonds.

Enzyme that catalyzes disulfide formation!

61
Q

What is Disulfide Isomerization? Why is it needed?

A

Proteins with multiple cysteine residues often require disulfide isomerization reactions before they attain their correct conformation

Oxidized PDI catalyzes the formation of disulfide bonds in substrate, PDI becomes reduced.
Reduced PDI aids rearrangement of disulfide bonds during folding. The first disulfides to form may not be correct for the native state, native disulfides are the most stable.
In both the reactions that take place, PDI forms mixed disulfide intermediates with a substrate. Don’t need to know all the steps.

Know that it is a stepwise mechanism!!

62
Q

How does PDI regeneration work?

A

It is a chemical cascade that regenerates oxidized PDI.

1) PDI becomes reduced after oxidizing the substrate

2) PDI is oxidized by Ero1 protein with cofactor FAD; Ero 1 is reduced

3) Ero1 is regenerated by FAD

4) FAD is regenerated by 02

63
Q

What is Calnexin and Calreticulin?

A
  • They both function together to ensure the proper folding of glycoproteins
  • They recognize glycan pattern on polypeptides (N-linked glycolysation)
  • They bind thioredoxin (ERp57 - Enzyme!)
  • They are highly homologous
64
Q

What are some differences between Calnexin (CNX) and Calreticulin (CRT)?

A
  • CNX has around 50 kDa lumenal domain and a TM helix anchor
  • CNX has a lumenal domain, but no THM helix, it has a signal fo retention in the ER
65
Q

What is the process of Calnexin Binding?

A

There is an N-linked glycan: branches mannose polymer with 3 glucose residues at the end.

The glucose and mannose are trimmed off step by step.

CNX specifically binds the glycan with 1 glucose, keeps the polypeptide in the ER.

If there is a single glucose, it is a signal for incomplete folding, but it is eventually removed.

66
Q

What is proteostasis?

A

Protein homeostasis or ‘proteostasis’ is the process that regulates proteins within the cell in order to maintain the health of both the cellular proteome and the organism itself.

67
Q

What is the Role of ER N-linked-glycosylation in proteostatis?

A
  • ensure proper folding of proteins through the calnexin/calreticulin cycle
  • Binds non-native polypeptides and reattaches a glucose to the glycan, CNX can bind again.
  • Native folded polypeptides are not recognized by UGGT.
  • glucosidase removes Glc from native and non-native polypeptides.
  • Mannosidase trims sugars further, UGGT does not recognize glycosylation.

1 and 2 glucose is trimmed and then you have the protien Clanexin that recognizes it with p57, then it is released and third protein also releases, hydrophobic resides are out there and recognized by other protein - UGGT.

68
Q

What are the 6 steps of the Calnexin and Calreticulin cycle?

A
  1. CNX keeps polypeptide in ER
  2. Glucosidase removes the last Glc
  3. UGGT restores Glc on misfolded polypeptides - CNX binding
  4. Folded polypeptides do not have Glc restored and exit to Golgi
  5. Mannosidase trims glycans without Glc (slow, irreverisble, proteins retained in ER by chaperones likely to get trimmed)
  6. Mannose-binding lectins (EDEM) select short glycans for degradation

The whole point of this cycle is to ensure proper protein folding.

69
Q

What is ERAD?

A

ER Associated Degradation

  • ERAD degrades both lumenal and transmembrane polypeptides
    Many substrates are misfolded protein: this if found through quality control, before proteins are sent to rest of the secretory pathway.
  • Also regulated degradation in response to signals, regulates metabolism.
70
Q

What is the first step of ERAD?

A
  • Substrates are recognized and brought to E3 Ub ligase complexes

A. Substrates which cannot fold are prevented from aggregating by BiP

B. BiP binds substrate in complex with specialized DNAJ (ERdj5) and lectin (EDEM)
a. ERdj5: J domain and thioredoxin domain
b. Catalyzes breakage of disulfide in substrate
c. reverse of PDI

C. Complex targets substrate to E3

71
Q

What is the second step of ERAD?

A
  • Targeting and export: Substrate Adaptors and E3 Ligases
  • Transmembrane E3 ligases (HRD1 and gp78) form complexes with substrate recognition adaptors:
    a. misfolded lumenal proteins (SEL1L)
    b. mannose-binding lectins (EDEM)
    c. misfolded TM proteins (erlin1/2, derlins)

Other interactions:
derlins
p97 receptors

72
Q

What is the the third step of ERAD?

A

Retro-translocation (reverse of translocation)

  • It is still in question whether there is a true pore, but there is regulated opening and closing which is pore-like. It is large enough to allow N-linked glycans.
  • Poly-ubiquitination in the cytosol is necessary
  • Large transmembrane E3 ligase complexes are thought to perform all these functions, HRD1 and gp78 E3 ligases.
  • Assisted by cytosolic protein p97/VCP
  • N-end rule, CHIP, SCF E3 are only in cytosol
73
Q

What is the p97 mechanism?

A
  • N-linked glycans and poly-Ub are too large to fit through the pore
  • p97 forms complexes with other proteins (Ub-binding adaptors, peptide:N-glycanase (PNGase) removes glycans, DUBs removes poly-Ub)
74
Q

what are some characteristics of p97?

A
  • Homo-hexamer of 97 kDa subunits
  • Uses ATPase energy to extract proteins from membrane
  • Substrate is also threaded through the central pore (hole)
75
Q

What is the 7 step summary of ERAD?

A
  1. Misfolded polypeptides are recognized by lectins and chaperones
  2. Disulfide bonds are broken by a thioredoxin DNAJ
  3. Adaptors bring misfolded polypepides to E3 ligases
    A. lectins, chaperones, lumenal and TM adaptors
  4. Transmembrane E3 ligases polyubiquitinate substrates and start retro-translocation
  5. p97 ATPase helps extract substrates from membrane
  6. Substrates are de-glycosylated (PNGase)
  7. Substrates are recognized by proteasome or shuttling receptors
76
Q

How do cells respond to stress that causes protein misfolding?

A

They increase their expression of chaperones and other specialized proteins.

1) Heat Shock Response (HSR)
- cytosolic and nuclear proteins
- protects against cell death

2) Unfolded Protein Response (UPR)
- ER proteins
- Can promote cell death if stress is too severe

77
Q

What is UPR?

A
  • It is ER Unfolded Protein Response

It is activated by the accumulation of unfolded proteins in the ER.
a. Reductive stress - breaks disulfide bonds
b. glycosylation inhibitors
c. loss of calcium

The transcription of ER chaperones, ERAD components, lipid synthesis is upregulated (allows the ER to expand in size)

Limited to ER - no overlap with HSR
Signalling has to cross ER membrane

78
Q

What happens if UPR response is insufficient?

A
  • Induces cell death
    called
    Apoptosis
79
Q

How many UPR signalling pathways are there? What are they called?

A
  • There are 3 UPR signalling pathways
    They are parallel

1) IRE1
2) PERK
3) ATF6

80
Q

What is common between the first 2 UPR signalling pathways?

A

They both need dimerization and then they start signalling.

81
Q

What is XBP1?

A

It is a transcription factor that up-regulates UPR genes.

82
Q

How does IRE1 work?

A
  • IRE1 has a lumenal domain, kinase, and RNase domains
  • It dimerizes in response to unfolded proteins (the misfolded proteins gives the signal to activate and says something is wrong)
  • Autophosphorylation activates RNAase activity (cut a specific RNA - XBP 1 mRNA has an intron so its peculiar)
  • IRE1 splices out 26 base intron frameshift allows XBP1s (spliced) to be translated efficiently
  • IRE1 and XBP1 work together!
83
Q

What is XBP1u?

A

It is the transcription factor but it is unspliced so it is translated at very low levels.
- IRE1 will splice out introns so then it can work more efficiently!!

84
Q

How is IRE1 activated?

A
  • Direct binding of unfolded protein by 2 IRE1 proteins causes dimerization
  • BiP (HSP70) binds inactive IRE1 and prevents dimerization
  • BiP binding to unfolded protein releases IRE1 to form dimers
  • Both mechanism activate IRE1

In response to ER stress, IRE1 is activated through a mechanism involving autophosphorylation, oligomerization and allosteric activation of a cytosolic endoribonuclease (RNAse) domain1

85
Q

What are a few characteristics about the PERK signalling UPR pathway? What transcription factor does it involve?

A
  • PERK has lumenal and kinase domains
  • PERK dimerizes upon stress and autophosphorylates - this is the same activation mechanism as IRE1
  • Phosphorylates translation factor to inhibit translation
  • ATF4 is the transcription factor
    It allows more expression of XBP1.
    CHOP - activates apoptosis genes.
    And it make decision to recover from stress or to commit to cell death.
86
Q

What is ISR? (Integrated Stress Response)

A

The integrated stress response is a cellular stress response conserved in eukaryotic cells that downregulates protein synthesis and upregulates specific genes in response to internal or environmental stresses

  • Involves eIF2alpha
  • Translation initiation factor eIF2alpha turns on general translation
  • phosphorylated eIF2 is inactive
  • eIF2alpha kinase responds to different stresses to inhibit translation; decreases amounts of unfolded new proteins, specia mRNAs including ATF4 are still translated to promote cell death.
    Involves some other kinases as well.
87
Q

Where is ATF6 normally and what is the process hat it involves?

A
  • It is a activating transcription factor
  • ATF6 is normally transmembrane at the ER - BiP binding site masks ER exit signal
  • upon stress, BiP is competed away by unfolded proteins

so then…

  • ATF6 is transported to the Golgi
  • Golgi proteases cleave off cytosolic domain ATF6 (N)
  • ATF6 (N) is a soluble transcription that up-regulated UPR genes

Bioc 212 (11 decks)

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