Derlin-1 retrotranslocation complex

Definition

Target type: cellularcomponent

A protein complex that functions in the retrotranslocation step of ERAD (ER-associated protein degradation), and includes at its core Derlin-1 oligomers forming a retrotranslocation channel. [GOC:bf, GOC:PARL, PMID:15215856, PMID:16186510]

The Derlin-1 retrotranslocation complex is a multi-protein complex that plays a crucial role in the removal of misfolded or damaged proteins from the endoplasmic reticulum (ER) lumen to the cytosol, where they can be degraded by the proteasome. This complex is composed of several components, including:
- **Derlin-1:** This protein is the central component of the complex and forms a channel through the ER membrane. It directly interacts with misfolded proteins and facilitates their translocation across the ER membrane. Derlin-1 is a transmembrane protein with a large luminal domain and a smaller cytosolic domain. The luminal domain contains a highly conserved motif known as the "Derlin domain," which is essential for its function.
- **Sec61 translocon:** The Sec61 translocon is a protein channel responsible for the translocation of proteins across the ER membrane during their synthesis. This complex is involved in the initial recognition of misfolded proteins and assists in their transfer to Derlin-1 for retrotranslocation.
- **Hrd1 ubiquitin ligase:** Hrd1 is an E3 ubiquitin ligase that plays a crucial role in the ubiquitination of misfolded proteins targeted for degradation. This ubiquitination process marks the proteins for recognition by the proteasome, ensuring their efficient removal from the cell.
- **Other accessory proteins:** Other accessory proteins, including the chaperones BiP and Grp170, contribute to the retrotranslocation process. These proteins assist in the folding of proteins and help prevent their aggregation in the ER lumen.
- **Cellular location:** The Derlin-1 retrotranslocation complex is located in the ER membrane, where it is positioned to interact with misfolded proteins in the ER lumen.
- **Mechanism of action:** When misfolded proteins are detected in the ER lumen, they bind to the Derlin-1 domain. This interaction triggers a conformational change in Derlin-1, opening a channel through the ER membrane. The misfolded protein is then threaded through this channel and delivered to the cytosol. Once in the cytosol, the protein is ubiquitinated by Hrd1 and degraded by the proteasome.
- **Significance:** The Derlin-1 retrotranslocation complex plays a critical role in maintaining ER homeostasis and preventing the accumulation of misfolded proteins. Dysregulation of this complex can lead to various diseases, including neurodegenerative disorders, cancer, and inflammatory diseases.
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Proteins (1)

Compounds (6)