Final answer:
Transmembrane proteins integrate into the membrane via N-terminal signal sequences and hydrophobic stop-transfer sequences during protein synthesis, with the N-terminus often facing outward. The process enables proteins to anchor in the membrane and span it multiple times.
Step-by-step explanation:
Integration of a TM Helix into the Membrane During Translation
The integration of a transmembrane (TM) helix into a cellular membrane during protein synthesis involves a specific interaction with the endoplasmic reticulum (ER). As ribosomes translate membrane proteins, they are directed to the rough ER (RER) by an N-terminal signal sequence. Once situated at the ER membrane, a stop-transfer sequence within the protein—a hydrophobic domain—inserts and anchors the growing polypeptide chain into the fatty acid interior of the membrane. This process can create proteins that span the membrane multiple times, with each pass governed by additional stop-transfer sequences. The orientation of these membrane proteins is determined such that the N-terminal end is typically facing the exterior of the cell.
Examples like glycophorin A illustrate how these TM helices are composed of hydrophobic amino acids, allowing them to integrate seamlessly into the lipid bilayer. Ongoing translation and the presence of multiple stop-transfer sequences contribute to the complex topology of these integral membrane proteins. After translation, proteins may undergo folding, modification, and targeting to their final destinations, with signal sequences acting as their 'train ticket' and being clipped off upon arrival.