Protein Folding Disorders Flashcards
What are the components of the cellular quality control system?
Proteasomes
Autophagy
ERAD (ER-associated degradation).
What are some abnormalities in protein folding?
Improper degradation
Improper localization
Dominant negative mutations
Gain-of-toxic function
Amyloid accumulation
You are studying protein folding and examine a group of cells that have overactive cellular degradation systems. What is the result of this?
mutant, misfolded, incomplete degraded proteins.
Incorrectly folded proteins lead to improper subcellular localization
loss-of-function
gain of function toxicity
What is a key modulator in protein homeostasis?
molecular chaperons
How does a mutant protein affect the function of wild-type protein?
It causes a loss of protein activity and interferes with the function of the protein at cellular and structural levels.
Protein conformational changes cause dominant phenotypes. What is the result of this?
Toxic proteins are made.
APOE4 disrupts mitochondrial function.
Superoxide dismutase is present
SRC kinases in cancer.
What are amyloid fibers?
Insoluble protein aggregates.
What is the sequence of amyloidogenic proteins?
VQIVY
It causes amyloid-related diseases
What do lower order oligomers cause?
Toxic effects.
Amyloid deposits could be a protective mechanism
What kind of structure do several amyloidogenic proteins form?
A pore like structure.
This disrupts the cell membrane integrity.
In what individuals are misfolded forms of the protein frequently observed in?
The elderly
Those with mutations in the protein early in life.
How do amyloids progess to amyloid plaques?
Seeding
Fibril formation
Deposit
What is a potential remediation process of amyloid buildup?
Blocking aggregate formation.
THis can be done with antibodies that recognize conformational changes and specific sequences.
How does hormetic stress affect an individual?
Applying moderate levels of stress could trigger beneficial and adaptive stress defense pathways, allowing longer life.
What is proteostasis?
Maintenance of protein homoeostasis.
What does proteostasis require?
Protein production
Folding
Degradation
What are unfolded protein responses?
Complex pathways to ensure proteostasis in different compartments.
They are found in the cytosol, ER and mitochondria
When is the apoptotic pathway used?
It is used last; it is the last line of defense.
What is heat shock repsonse?
A response that manages denatured proteins in the cytosol.
What are the two major mitochondrial chaperone systems?
mtHSP70
Multimeric protein HSP60 - HSP10
How many proteins of the ETC are encoded by mtDNA?
13
What are protein quality control proteases?
They recognize and degrade the proteins that do not fold.
They are also properly assembled.
What is the functio of UPRmt?
It senses the overload of the QC system capacity.
It activates the transcription of nuclear encoded protective genes and re-establishes the mitochondrial homeostasis.
What is a limitation of the UPRmt signaling?
The signal transmission from the unfolded/misfolded mitochondrial proteins to the nucleus cannot be accomplished using HSR and UPR system.
What system assists in signal transmission from the unfolded/misfolded mitochondrial proteins to the nucleus?
retrograde response
