Stop Transfer Sequences Mediate the Insertion of Integral Membrane Proteins

Question 1

what is the other major group of polypeptides synthesized on the rough ER (what are they destined to become)

Answer 1

molecules destined to become integral membrane proteins

Question 2

how do these molecules “destined to become integral membrane proteins” become integral membrane proteins?

Answer 2

completed polypeptide chain remains embedded in the ER membrane rather than being released into the ER lumen

Question 3

two main mechanisms postulated for these molecules becoming integral membrane proteins…

1. polypeptides with an ER signal sequence at their N-terminus
   - what does this allow?
   - elongation of the polypeptide chain then continues until..?
   - what does the stop transfer sequence do? (3)

Answer 3

• allows an SRP to bind the ribosome mRNA complex to the ER membrane
• elongation of the polypeptide chain then continues until the hydrophobic transmembrane domain (functions as a stop transfer sequence) is synthesized
• –> stop transfer sequence halts translocation of the polypeptide through the ER membrane
• –> tanslocation continues, the rest of the polypeptide stays on the cytosolic side of the ER membrane
• –> stop transfer sequences moves laterally, forming a permanent transmembrane segment

Question 4

two main mechanisms postulated for these molecules becoming integral membrane proteins…

2. membrane proteins without a typical signal sequence at the N-terminus
   - preforms 2 functions…
   - first acts as an…? which allows?
   - then its hydrophobic region functions as a…? and does what?
   - the orientation of the start transfer sequence at the time of insertion determines…?

Answer 4

• instead posses internal start transfer sequence that performs two function:
  1. first, acts as an ER signal sequence that allows an SRP to bind the ribosome mRNA complex to the ER membrane,
  2. then its hydrophobic region functions as a membrane anchor that moves out through a side opening in the translocon and permanently attaches the polypeptide to the lipid bilayer
• the orientation of the start transfer sequence at the time of insertion determine which terminus of the polypeptide ends up in the ER lumen and which in the cytosol