How translocation of secretory proteins takes place across the ER membrane?

The translocation of secretory proteins across the endoplasmic reticulum (ER) membrane is a crucial step in the secretory pathway. This process ensures that newly made proteins enter the lumen of the rough ER, where they begin their journey toward secretion or membrane insertion.

Secretory proteins are synthesized by ribosomes in the cytosol. However, those meant to enter the ER begin their synthesis with a special short sequence of amino acids called a signal peptide at their N-terminal end. This signal peptide acts as a tag, directing the ribosome to the ER.

As soon as the signal peptide emerges from the ribosome, it is recognized by a complex known as the Signal Recognition Particle (SRP). The SRP binds to the ribosome and signal peptide, temporarily pausing protein synthesis. This pause is necessary to guide the ribosome to the ER membrane without the protein being fully synthesized in the cytosol.

The SRP-ribosome complex then docks on the ER membrane by binding to the SRP receptor, which is located on the cytoplasmic side of the ER. After this docking, SRP is released and the ribosome aligns with a protein-conducting channel on the ER membrane called the translocon.

Once the ribosome is properly positioned on the translocon, protein synthesis resumes. The growing polypeptide chain is threaded directly into the ER lumen through this channel. This process is known as co-translational translocation, because translation and translocation happen at the same time.

Inside the ER lumen, the signal peptide is usually removed by an enzyme called signal peptidase. The protein may then fold into its correct shape, assisted by chaperone proteins such as BiP. In many cases, additional modifications like glycosylation may also begin in the ER.

Therefore, the translocation of secretory proteins across the ER membrane is a highly controlled process involving signal peptides, SRP, SRP receptor, translocon and other proteins. It ensures that secretory proteins are correctly inserted into the ER lumen as they are being synthesized.








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