Protein Sorting & Transport PART 2

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I am Dr. Rinkal Mulani,
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Today's video is all about the fascinating topic of the protein sorting and transport. Specifically, we will explore the...................
Proteins can be translocated into the ER either during their synthesis on membrane-bound ribosomes (cotranslational translocation) or after their translation has been completed on free ribosomes in the cytosol (posttranslational translocation).
In mammalian cells, most proteins enter the ER cotranslationally, whereas both cotranslational and posttranslational pathways are used in yeast.
The first step in the cotranslational pathway is the association of the ribosome–mRNA complex with the ER.
Ribosomes are targeted for binding to the ER membrane by the amino acid sequence of the polypeptide chain being synthesized, rather than by intrinsic properties of the ribosome itself.
Secretory proteins are targeted to the ER by a signal sequence at their amino (N) terminus, which is removed during incorporation of the growing polypeptide chain into the ER.
This was demonstrated by experiments showing that translation of secretory protein mRNAs on free ribosomes yielded proteins that retained their signal sequences and were therefore slightly larger than the normal secreted proteins.
However, when ER vesicles were added to the system, the growing polypeptide chains were incorporated into the vesicles and the signal sequences were removed by proteolytic cleavage
The signal sequences span about 15–40 amino acids, including a stretch of 7–12 hydrophobic residues, usually located at the amino terminus of the polypeptide chain
Cotranslational targeting of secretory proteins to the ER
Step 1: As the signal sequence emerges from the ribosome, it is recognized and bound by the signal recognition particle (SRP).
Step 2: The SRP escorts the complex to the ER membrane where it binds to the SRP receptor.
Step 3: The SRP is released, the ribosome binds to the translocon, and insertion of the signal sequence opens the translocon.
Step 4: Translation resumes and the signal sequence is cleaved by signal peptidase.
Step 5: Continued translation drives translocation of the growing polypeptide chain across the membrane.
Step 6: The completed polypeptide chain is released within the ER lumen.
As they emerge from the ribosome, signal sequences are recognized and bound by the signal recognition particle (SRP) consisting of six polypeptides and a small cytoplasmic RNA (SRP RNA).
The SRP binds the ribosome as well as the signal sequence, inhibiting further translation and targeting the entire complex (the SRP, ribosome, mRNA, and growing polypeptide chain) to the rough ER by binding to the SRP receptor on the ER membrane (Figure 12.6).
Binding to the receptor triggers the hydrolysis of GTP bound to the SRP, releasing the SRP from both the ribosome and the signal sequence of the growing polypeptide chain.
The ribosome then binds to a protein translocation complex or translocon in the ER membrane, and the signal sequence is inserted into a membrane channel.
Key insights into the process of translocation through the ER membrane came from determination of the translocon structure by Tom Rapoport and his colleagues in 2004.
In both yeast and mammalian cells, the translocons through the ER membrane are complexes of three transmembrane proteins called the Sec61 proteins
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