Protein folding in health and disease Flashcards
What does the structure of an alpha helix look like?
Where the DNA chain twists together
What does the structure of a beta-pleated sheet look like?
Where the chain folds back on itself or where 2 regions of the chain lie parallel to one another
What bonds are involved in secondary protein structure?
Hydrogen bonding between atoms along polypeptide backbone
What bonds are involved in the tertiary protein structure?
Forces between the R groups
Ionic bonds- from positively and negatively charged R groups (from acidic and basic groups that ionise)
Polar forces- hydrophilic/piolar make hydrogen bonds with one another
Covalent bonds- sulfur atoms in certain R groups
What is a quaternary structure made of?
Made of more than one polypeptide chain
What bonds are involved in the quaternary protein structure?
Same as tertiary between the polypeptides: hydrophobic, hydrophilic, covalent, ionic
What is a translocon?
Protein pore in the ER membrane through which new synthesised proteins go through
Makes sure transmembrane proteins put in the right place
How is an amino acid chain threaded though translocon? (steps)
Ribosome sits on top of translocon
New protein chain as getting translated is inserted into translocon
Signal recognition particle binds to the sequence of newly synthesised peptide as emerges from ribosome
SRP then binds to SRP receptor on ER membrane
New peptide chain inserted into translocon channel where enters ER
Chain moves its way round and out again as its a single pass trans membrane protein
Steps of CFTR synthesis
1) Transcription in nucleus 2 Translation and protein folding 3) Post- translation modification in golgi 4) Protein trafficking 5) Surface expression
What does the endocytic pathway do?
It removes membrane bound proteins from cell surface
Either gets recycled back to cell membrane
Targeted for degradation
Type 1 CF type of mutation, RNA and CFTR Protein
Nonsense mutation, frameshift
Unstable truncated RNA
Absent functional CFTRR
Type 2 CF type of mutation, RNA and CFTR Protein
Missense, aminoacid deletion Full-length CFTR RNA Protease destruction of misfolded CFTR (cant go through golgi) CFTR Trafficking defect Absent functional CFTR
Type 3 CF type of mutation, RNA and CFTR Protein
Missense, amino acid change
Full length CFTR RNA
Nascent CFTR
Defective channel regulation- CFTR channel doesnt open and allow chloride ions through
Type 4 CF type of mutation, RNA and CFTR Protein
Missense, amino acid change
Full length CFTR RNA
Nascent CFTR
Defective CFTR channel conduction, Decreased channel conductance- reduced flow of chloride ions through CFTR channel
Type 5 CF type of mutation, RNA and CFTR Protein
Splicing defect, missense Make correct/incorrect RNA Scarce nascent CFTR Scarce functional CFTR Reduced synthesis of CFTR
Type 6 CF type of mutation, RNA and CFTR Protein
Missense, amino acid change
Nascent CFTR
Decreased CFTR membrane stability
Quickly get endocytosed into cell and degraded
Which mutation reduces the protein function?
Class 3 and 4
Which mutation reduced the amount?
Class 1,2,5,6 mutation
Potentiators are given to what mutations?
If have reduction in protein function (class 3 and 4)
Correctors and production correctors are given to what mutations?
Class 1,2,5,6 mutations where there is reduced amount
How do potentiators work?
Increase the activity of defective CFTR at the cell surface
How do correctors work?
Improve processing and delivery of functional CFTR protein to the cell surface. Overcome defective protein processing that normally results in production of misfolded CFTR. Increase amount of CFTR protein at cell surface.
Allows increase trafficking of CFTR to plasma membrane
Will also stop protein being degraded and help transport it to cell membrane
How do production corrects work?
Instruct ribosomes to read through premature termination codons during mRNA translation. Allowing protein to be made.
What is an example of a potentiator?
Ilvacaftor=Kaleydeco
What is an example of a corrector?
Lumicaftor
What is the best treatment at the moment?
Orkambi
Ivacaftor + Lumicaftor
Treatment of alzheimers
Acetycholinesterase inhibitors
Increased concentration of acetylcholine leads to increased communication between nerve cells
