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
