The ER Flashcards
What is the primary function of the endoplasmic reticulum (ER)?
The ER is involved in protein modifications, folding, and quality control.
What process allows soluble proteins to be released into the ER lumen?
Co-translational translocation.
What is the role of the Sec61 translocator in protein insertion?
It opens a channel for the polypeptide to be threaded through as translation occurs.
Fill in the blank: The _______ is cleaved by signal peptidase, releasing the protein into the ER lumen.
signal sequence
What stabilizes the folded structure of proteins in the ER?
Disulfide bonds formed by oxidation of cysteine side chains.
True or False: N-glycosylation occurs on serine residues in the ER.
False
What is the consensus sequence for N-glycosylation?
Asn-X-Ser or Asn-X-Thr (X = any residue except Proline).
List three functions of N-glycosylation.
- Assists protein folding
- Modified to create mannose-6-phosphate tags which act as a lysosome sorting signal
- Acts as a ligand for specific cell-cell recognition events
What type of proteins does the ER quality control retain?
Misfolded proteins.
What triggers the Unfolded Protein Response (UPR) in the ER?
Build-up of misfolded proteins in the ER lumen.
What is the role of molecular chaperones in the ER?
They assist in the proper folding of newly synthesized polypeptide chains.
How do transmembrane proteins anchor in the lipid bilayer?
Through additional hydrophobic sequences.
What is the significance of the ER being the entry point for the secretory pathway?
It is where proteins destined for the Golgi, lysosomes, and plasma membrane are synthesized.
Fill in the blank: The ER lumen is _______ which aids in disulfide bond formation.
oxidizing
What happens to proteins with a signal sequence when they encounter the ER?
They are targeted and imported into the ER.
What method is used to analyze radioactive proteins to confirm signal cleavage?
SDS-PAGE.
True or False: The orientation of membrane proteins is fixed after insertion.
True
What happens to proteins that cannot fold correctly in the ER?
They are retained by ER quality control mechanisms.
What role does BiP play in the ER?
It binds exposed hydrophobic residues and prevents aggregation to allow proteins more time to get into the right conformation
What type of vesicles transport proteins along the secretory pathway?
Membrane-bound transport vesicles.
How do hydrophobic sequences anchor transmembrane proteins in the lipid bilayer?
- Signal sequence binds Sec61 = channel opens
- Hydrophobic stop-transfer sequence stops the movement of the polypeptide through the channel
- Stop-transfer sequence is released from the channel into the bilayer, forming a transmembrane domain
- Signal sequence is cleaved
- Protein is inserted into the bilayer, orientation is fixed at the N-terminus in the lumen
What do multi-pass transmembrane proteins have?
An internal ER signal sequence instead of an N-terminus sequence
Known as the start-transfer sequence
Role of start-transfer sequence
- Start-transfer sequence acts as an ER targeting signal
- Binds to Sec61 and opens the channel to start translocation
- The polypeptide moves through the channel
- Stop-transfer sequence enters the channel and stops translocation
- Both hydrophobic sequences are released from the channel, forming transmembrane domains
- Alternating start and stop transfer sequences generate complex multi-pass membrane proteins
- Signals do not get cleaved
Ways membrane protein can associate with the lipid bilayer
- transmembrane
- monolayer associated
- lipid linked
- protein attached
