ER-Retention of the Protein:
The C-terminal KDEL sequence in a protein plays a crucial role in ensuring its ER-retention. The KDEL sequence acts as a signal for the retrieval of proteins from the Golgi apparatus to the endoplasmic reticulum (ER). This sequence is recognized by specific receptor proteins located in the ER called KDEL receptors. The KDEL receptor binds to the KDEL sequence and retrieves the protein from the Golgi apparatus, preventing its secretion.

Mechanism:
When a protein containing a C-terminal KDEL sequence is synthesized, it is initially transported from the ER to the Golgi apparatus. However, the KDEL receptor recognizes the KDEL sequence and binds to it. This binding triggers the formation of a vesicle that transports the protein back to the ER. This retrieval mechanism ensures that the protein remains in the ER and prevents its secretion into the extracellular space.

Importance of ER-Retention:
The ER is responsible for protein folding, quality control, and post-translational modifications. By retaining the protein in the ER, the C-terminal KDEL sequence ensures that the protein undergoes proper folding and modifications before it is transported to its final destination within the cell. This ensures the protein's functionality and prevents the accumulation of misfolded or defective proteins in the cell.

Role in Protein Trafficking:
In addition to ER-retention, the C-terminal KDEL sequence also plays a role in protein trafficking. It helps regulate the localization of proteins within the cell by controlling their movement between the ER and the Golgi apparatus. Proteins that require further modifications or sorting are retained in the ER, while those ready for secretion or targeting to other organelles are allowed to exit the ER.

Conclusion:
In summary, the presence of a C-terminal KDEL sequence in a protein ensures its ER-retention by interacting with KDEL receptors. This retention is essential for proper protein folding, quality control, and trafficking within the cell. The C-terminal KDEL sequence acts as a molecular signal that prevents the secretion of the protein and facilitates its retrieval from the Golgi apparatus back to the ER.