Term
| Nascent proteins go to 4 places off free ribosomes in cytosol |
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Definition
A) Cytosol
B) Mitochondria
C) Endoplasmic Reticulum
D) Nucleus |
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Term
| How does the cell know where to transport protein? |
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Definition
| Two types of signals can be recognized in protein targeting: 1) a linear sequence of amino acids, and a 2)patch formed by a 3D structure. |
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Term
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Definition
1)Regulates protein folding to ensure protein folds properly and also has the ability to tag proteins for degradation.
2)Uses energy to stabilize protein through its intermediates to make sure it reaches its native form.
3)minor point: also implicated in protein aggregation.
Hsp90--ATPase activity |
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Term
| Some diseases of protein aggregation (7; hint almost all of them are neurological) |
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Definition
A) Alzheimer’s disease
B) Parkinson’s disease
C) Huntington’s disease
D) Amyotrophic lateral sclerosis (ALS)
E) Creutzfeldt–Jakob disease (Mad Cow's Disease)
F) Senile systemic amyloidosis;cardiomyopathy
G) Type II diabetes |
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Term
| Name some diseases of protein mis-folding (6) |
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Definition
A) Cystic fibrosis (CFTR)
B) Marfan syndrome (Fibrillin)
C) Fabry disease (α-galactosidase)
D) Gaucher’s disease (ß-glucocerebrosidase)
E) Retinitis pigmentosa (rhodopsin)
F) Cancer (P53) |
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Term
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Definition
| If sequence has more hydrophobic AAs, it would have an easier time to get across the membrane. |
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Term
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Definition
RAN
1)Part of the Ras family.
2)GTP binding proteins.
3)Involved in import and export of proteins to and from nucleus.
*Binds to Nuclear Import Receptor and releases protein inside nucleus* |
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Term
| Kennedy’s disease (Spinal bulbar muscular atrophy) |
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Definition
1)X-linked
2)Throat problems (breathing, swallowing, jaw drop)
3)Muscle weakness
4)Muscle twitching
5)Infertility
6)Symptoms begin in late 30s
7)Familial
*Part of PolyGlutamine Diseases, think Huntington's.* *AR binds to RAN which allows for transcription. Normally, poly AR impairs binding to RAN and instead poly AR aggregates.*
*Hsp90 inhibitors can degrade polyQ AR preventing its aggregation and toxicity.* |
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Term
| Secretory pathway: signal peptide recognition |
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Definition
Step A:
SRP (signal recognition protein) binds to signal sequence which temporally halts transcription.
Step B:
SRP and growing peptide are recruited to surface of ER.
Step C:
Docking protein binds to SR
Step D:
SRP protein binds to ribosome while translation resumes. Peptide is synthesized in ER membrane and after ribosome disassociates, signal peptidase cleaves the signal sequence and protein is now released into the ER lumen and free to go where it has been tagged to go. |
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Term
| Synthesis of a transmembrane protein with the C-terminus facing the cytosol |
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Definition
1)Sequence (e.g.: enconding for ribosome) binds to start-transfer peptide binding site and undergoes translation.
2)Once stop-transfer sequence reaches its peptide binding site, signal peptidase cleaves the (start-transfer) signal sequence.
3)Translation resumes and now growing strand (C-terminus) is inside cytosol and N-terminus is inside ER lumen. Start and stop-transfer sequences remain embedded in ER membrane. |
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Term
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Definition
1)cystic fibrosis transmembrane conductance regulator (CFTR)--autosomal recessive disease
2)Huge transmembrane chloride channel
3)Mutations in this gene lead to disease (70% are ∆F508-This deletes Phe at 508
4)Only 25% of this protein is ever properly folded
5)Only need ~5% to maintain functionality
6)The one Phe deletion makes the ER think that the CFTR is not folded properly, and this marks it for degradation by ER-associated degradation (ERAD)
7)Mutant CFTR can still be active despite the mutation *by depleting Aha1 levels!* |
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Term
| Why Sugar On Proteins? (4) |
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Definition
1)Structure
2)Targeting
3)Interactions
4)Other post-translational modifications |
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Term
| N-linked glycosylation on surface of ER |
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Definition
1)GlutNAc OR GalNAc (attached to surface of ER--may be some phosphates--ER membrane protein=dolichol, *this should sound familiar!*) at base of every sugar.
2)Sugar can also attach independently either to another sugar or straight to the ER membrane.
3)It is the Asparagine (N, makes sense since it is N-linked) residue that GluNac or GalNac will attach to on the growing peptide strain inside the lumen of the ER. This will effectively affect the structure of the protein (as opposed to tagging it after translation). |
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Term
| Diseases caused by glycosylation defects |
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Definition
1) Congenital Muscular Dystrophies
2) Walker–Warburg syndrome
a)muscle–eye–brain disease
b)Fukuyama muscular dystrophy
c)Inclusion Body Myopathy 2
3)Congenital Dyserythropoieic Anemia Type II
4)Congenital Disorders of Glycosylation, Types I & II |
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Term
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Definition
1)Proteins imported into the mitochondrial matrix can form an N-terminal amphipathic helix, which is positively charged on one side and hydrophobic on the other.
2)Peptide binds to TOM complex. TIM23 interacts and forms a channel for protein insertion into the matrix.
3)You have cleavage by signal peptidase, and you now have a mature mRNA. |
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Term
| Parkinson’s disease linked to ___________ |
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Definition
Mitochrondria.
1)Dysfunction of mitochondria (e.g.: ROS, Oxygen consumption, ATP synthesis, calcium regulation) leads to neurodegeneration.
2)PINK1; PTEN induced putative kinase 1
AKA: PARK6 (all Parkinson disease names are called PARK)
3)You have a)mitochondrial targeting region and b)kinase domain.
4)Mutations in the targeting region from polar to non-polar AAs (i.e.: P and F) may inhibit peptide from reaching mitochondria. |
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Term
| Plasma Membrane Transport |
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Definition
1)Mutations in the GTPase K-Ras are linked to:
a)Leukemia
b)Colon cancer
c)Pancreatic cancer
d)Lung cancer
2)K-Ras transduces EGFR signaling, a growth factor receptor
3)Modulation of the association of K-ras with the plasma membrane could affect activity. |
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Term
| Sialylation in the PM occurs on N-acetylgalactosamine (GalNAc) chains |
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Definition
1)Salycic acid group of Neuraminidase cleaves lipidated portion of GalNAc from receptor.
2)Inhibition of neuraminidase (with neuraminidase inhibitors) prevents release of virion from cell surface and thus halts viral replication. |
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Term
| Lysosomal Targeting (3 steps) |
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Definition
No signal sequence! Instead
1)Oligosaccharides in targeting: generation of a signal for lysosomal targeting. Note that the recognition sequence is not a linear stretch of amino acids.
Enzyme 1 is UDP-GlcNAc phosphotransferase.
2)phosphodiesterase removes the GlcNAc, leaving a phosphate on one of the mannose residues. This is the recognition signal for sorting to the lysosome.
3)Incorporation of proteins into lysosomes involves forming a recognition tag with mannose-6-phosphate. The mannose-6-phosphate receptor is a type of lectin (CHO binding protein). |
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Term
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Definition
Also called I-Cell Disease
-These children have a defect in GlcNAc phosphotransferase, the enzyme that normally allows coupling to mannose-6-phosphate which is required for processing from the Golgi to the lysosome
SO you have elevated levels of elevated levels of lysosomal enzymes in serum. |
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Term
| What happens if a protein does not have a signal sequence? |
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Definition
| I thought they get degraded BUT the answer is, **they stay in the cytosol.** Gotta have some fun making these flashcards. Also, if you are reading this, thanks for taking the time :). |
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