Protein folding, processing and sorting Flashcards
Where are polypeptide chains synthesised?
In the ribosome tunnel
How many amino acids can fit inside the tunnel in a human ribosome?
~20
What arrangement does the polypeptide chain form in the ribosome tunnel? What happens when it leaves the tunnel?
In a linear format inside the tunnel (due to space constraints)
Once out of the tunnel it immediately folds
Why does the amino acid fold over once it leaves the ribosome tunnel?
It goes from a non-polar environment inside the ribosome to a polar environment in the cytoplasm therefore tries to re-arrenge itself so that the non-polar side chains are on the inside and the polar side chains on the outside
What shapes can the polypeptide chain fold into to optimise its arrangement in the polar environment?
α helix (coil) or a ß sheet (primary chain zig zags forming a pleat sheet)
How are the α helix and ß sheets stabilised?
By hydrogen bonds
What kind of structure are α helix and ß sheets?
Secondary structures
What side chains makes amino acids non-polar? What is on these side chains that makes them non-polar? How does this impact their response in the polar environment of the cytoplasm?
R group
H, CH3 or multiple bonded CH2+
Causes this group to be hydrophobic
What side chains makes amino acids polar? What is on these side chains that makes them polar? How does this impact their response in the polar environment of the cytoplasm?
R group
OH-, SH or an amide ( -C=O,NH2)
Causes this group to be hydrophilic
What side chains makes amino acids electrically charged? What is on these side chains that makes them electrically charged? How does this impact their response in the polar environment of the cytoplasm?
R group
Acidic or basic groups
Acid = carboxyl group (COO-), basic = amino group
What kind of structure do secondary structures get turned into?
Tertiary structures
How are tertiary structures made?
Secondary structures are folded over by other proteins
What are the forces involved in holding the shape of a tertiary structure? What parts of the protein do they bond? Are these weak or strong?
Hydrophobic collapse (poorly understood force…)
Van Der Waals forces between non-polar amino acid side chains (weak)
Hydrogen bonds between polar amino acid side chains (strong)
Ionic bonds between charged amino acid side chains (weak)
Disulphide bridges between cysteine molecules (strong - is covalent FYI)
What is the shape of a tertiary structure?
A more globular protein
What is the structure that tertiary proteins may turn into?
Quaternary structures
What are the two types of quaternary structures?
Homodimer or Heterodimer complex
What is a homodimer? What is a heterodimer complex?
Homodimer = 2 + of the same proteins being put together
Heterodimer complex = 2 + different proteins put together
What happens if there is a mistake in the mRNA for the protein? How does this affect the tertiary/quaternary structure?
Substitutes in a different amino acid
This can result in the proteins being folded differently
What amino acid is important for creating covalent bonds in the tertiary/quaternary structures? What happens if this amino acid is not present due to incorrect translation?
Cystine - form disulphides bonds
The complex won’t hold therefore it won’t fold over properly
What happens to the functionality of the protein if it is not folded properly?
Alters the shape of the binding groove which alters how the target molecules can bind to the binding groove therefore how efficiently it can degrade the molecule
Once the polypeptide is released into the cytoplasm, how does it know where to go for further processing/utilisation?
The front end of the polypeptide is a signal peptide
What are the two different types of proteins that are processed differently?
Secretory proteins - fully translocated into the ER
Membrane protein - 1+ hydrophobic segments of polypeptide chain anchor it in bilayer
Explain how the polypeptide begins the process for folding
1 - first few amino acids are recognised by a translocating protein
2 - the translocating protein takes the polypeptide and takes it into one of the pores on the rough ER
3 - The signal peptide is removed from the polypeptide
4 - the polypeptide chain is inserted into the endoplasmic reticulum lumen to be folded
Where is the signal peptide found on the polypeptide?
At the N-terminus
What happens to the folded polypeptide chain after processing in the ER?
Goes to the golgi body for further processing then either get secreted, goes into one of the intracellular organelles or onto the membrane
What is phosphorylation?
The addition of a phosphate group onto a proteins
When is post translational modification done?
Following transcription and translation
Post translational modification is heavily controlled for what kind of proteins?
Signal proteins
What are some of the post translational modifications that can be done to a protein?
Methylation (addition of a methyl group)
Acetylation (addition of an acetyl group)
Biotinylation (addition of biotin)
Carboxylation (addition for carboxylic acid group)
Carbohydrate addition (addition of carbohydrate, particularly for membrane bound proteins FYI)
