The ER membrane is continuous with what structure within a cell?
Nuclear envelope.
What are the two types of ER?
State what both sites synthesise.
- RER - ribosome covered tubules, site for protein synthesis.
- SER - shorter tubules, site for lipid synthesis.
What are the four main functions of the SER?
Acronym: sally sea-shells dies.
- Synthesis of lipids and cholesterol for cell membranes.
- Synthesis of steroid hormones.
- Storage and release of calcium ions.
- Detoxification: getting rid of toxic molecules in the body.
The RER is the site of protein synthesis and processing for which three types of proteins?
- Transmembrane proteins.
- Proteins destined for the ER, golgi body, plasma membrane, lysosomes and endosomes.
- Proteins to be secreted to the cell exterior.
Some proteins are not processed in the ER. What are these proteins are there are they instead processed?
Cytosolic proteins - processed on cytosolic ribosomes.
How is the cytosolic protein synthesised in the cytosol?
- Common pool of ribosomal subunits in the cytosol.
- Ribosomal subunit binds to mRNA 5’ end.
- Formation of a free polyribosome in cytosol (multiple ribosomal subunits synthesise the mRNA).
- Protein in synthesised.
How is a protein destined to be a transmembrane protein/hormone synthesised?
simple overview
- Common pool of ribosomal subunits in the cytosol.
- Ribosome subunit binds to mRNA 5’ end.
- During protein synthesis, the ribosome-mRNA complex is moved to the ER membrane.
- Protein is embedded or transferred into the ER.
Co-translational translocations allows proteins to be imported to the ER while they are undergoing what biological process?
Protein synthesis.
How does a protein remain in its primary structure during co-translational translocation?
One end of the polypeptide attaches to the ribosome, whilst the other inserts itself into the ER.
What do chaperone proteins do?
Why is it unnecessary for a chaperone protein to be present in co-translational translation?
Chaperone proteins prevent target proteins from being damaged and folding into their tertiary structure.
As the target protein in co-translational translocation is in its primary structure and held in it by a ribosome and the ER, a chaperone protein is not needed.
The signal sequence of a protein can be found at what terminal?
N terminal.
For co-translational translocation the signal sequence must be recognised by what two structures?
- SRP (signal recognition particle).
2. ER - must be embedded within the ER membrane.
The SRP recognises the signal sequence on the N terminal of the growing polypeptide.
What two things do the SRPs bind to?
- Signal sequence.
2. Ribosome.
The binding of a SRP to the signal sequence and ribosome causes what?
Synthesis of the polypeptide to pause momentarily.
What part of the SRP pauses synthesis of the polypeptide?
Translational pause domain.
SRP consists of RNA and how many proteins?
6
Describe how SRPs facilitate the protein synthesis of a protein destined to enter the ER lumen.
complex explanation
- Protein is synthesised by the ribosome, forming the N terminal (signal sequence).
- SRP binds to signal sequence and its translational pause domain binds to the ribosome.
- Synthesis pauses.
- SRP moves towards the ER membrane and binds to a SRP receptor.
- Binding to the SRP receptor (next to the protein translocator) allows protein to move into the central lumen of the protein translocator.
- Complex is disassembled and SRP and its receptor are released from target protein.
- Ribosome and protein remain bound with the membrane, until protein is released into the ER lumen.
Describe what a polysome is.
mRNA remains bound to the ER as it is translated by multiple ribosomes at once.
Once a protein has been translated and is inside the ER, it is folded into its 3D conformation by what bonds?
List 3.
- Ionic bonds
- Hydrogen bonds
- Van der Waals attraction
- Disulphide bonds
What happens during N-linked protein glycosylation?
Pre-formed precursor oligosaccharide, composed of 14 sugars, is added to proteins via the N-terminus (amine group) of an asparagine side chain.
What is the importance of N-linked protein glycosylation?
Quality control - ensures the protein has been folded correctly and is hence mature.
If a protein has not folded correctly, what two processes may occur?
- 3x glucose and 1x mannose are cleaved from the oligosaccharide.
- Glucosyltransferase enzymes add a single glucose back.
Addition of glucose binds protein to chaperones to prevent aggregation and gives them another opportunity to fold.
Describe the process that happens when a protein tries to fold correctly, include the addition of glucose and use of enzymes.
- Protein containing one glucose binds to calnexin (chaperone).
- Protein released and glucosidase cleaves the glucose.
- Protein tries to fold.
- Cycle repeats - if protein does not fold correctly, it is degraded.
Accumulation of misfolded proteins causes ER stress and triggers an unfolded protein response. What three things could happen?
- Inhibition of protein synthesis.
- Degrading of misfolded proteins at a faster rate.
- Increase of transcription of chaperones to look after misfolded proteins.
