protein insertion into ER membrane by stop-transfer membrane-anchor sequence

Definition

Target type: biologicalprocess

A process of protein insertion into the endoplasmic reticulum (ER) membrane in which stop-transfer membrane-anchor sequences become an ER membrane spanning helix. [ISBN:0716731363]

Protein insertion into the endoplasmic reticulum (ER) membrane via a stop-transfer membrane-anchor sequence is a crucial process for the localization and function of transmembrane proteins. This mechanism involves a series of steps, starting with the translation of the mRNA encoding the target protein on ribosomes in the cytoplasm.

As the nascent polypeptide chain emerges from the ribosome, it encounters a signal sequence at its N-terminus. This signal sequence directs the ribosome to the ER membrane and initiates the process of translocation. The signal sequence binds to the signal recognition particle (SRP), which escorts the ribosome-mRNA complex to the ER membrane.

At the ER membrane, the ribosome interacts with the translocon, a protein channel embedded in the ER membrane. The signal sequence is cleaved by a signal peptidase, and the growing polypeptide chain begins to translocate through the translocon.

During this translocation, a hydrophobic stop-transfer membrane-anchor sequence within the polypeptide chain emerges from the translocon. This sequence interacts with the hydrophobic core of the ER membrane and becomes embedded within it, halting further translocation of the polypeptide chain.

The stop-transfer sequence serves as a transmembrane anchor, anchoring the protein within the ER membrane. The portion of the protein that was already translocated remains in the ER lumen, while the remaining portion, containing the stop-transfer sequence, is embedded in the membrane.

The orientation of the protein within the membrane is determined by the position of the stop-transfer sequence. If the stop-transfer sequence is located near the C-terminus of the protein, the N-terminus will face the ER lumen, and the C-terminus will be located in the cytoplasm. Conversely, if the stop-transfer sequence is located near the N-terminus, the C-terminus will face the ER lumen, and the N-terminus will be in the cytoplasm.

Once the protein is anchored in the membrane, the ribosome dissociates, and the translocon closes. The protein can undergo further processing and modifications within the ER, such as glycosylation or folding, before being transported to its final destination in the cell.'
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Proteins (1)

Compounds (1)