EDEM2

EDEM2

Crystal structure of EDEM2 protein.

EDEM2 (ER degradation-enhancing alpha-mannosidase-like protein 2) is a protein involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. It is a member of the EDEM family of proteins, which also includes EDEM1 and EDEM3. EDEM2 plays a crucial role in recognizing and targeting misfolded glycoproteins for degradation, thereby maintaining the quality control of protein folding in the ER.

Structure

The EDEM2 protein consists of several functional domains that contribute to its role in ERAD. It contains a luminal domain, a transmembrane domain, and a cytoplasmic domain. The luminal domain is responsible for recognizing and binding to misfolded glycoproteins, while the transmembrane domain anchors EDEM2 to the ER membrane. The cytoplasmic domain interacts with other ERAD components, facilitating the degradation process.

Function

EDEM2 acts as an ERAD factor by recognizing and targeting misfolded glycoproteins for degradation. It specifically recognizes glycoproteins with high-mannose oligosaccharides, which are indicative of protein misfolding. Upon binding to these misfolded glycoproteins, EDEM2 recruits other ERAD components, such as the E3 ubiquitin ligase HRD1, to facilitate their retrotranslocation from the ER lumen to the cytosol. Once in the cytosol, the misfolded glycoproteins are ubiquitinated and degraded by the proteasome.

Role in Protein Quality Control

Protein folding is a complex process that occurs in the ER, and the quality control mechanisms in place ensure that only properly folded proteins are allowed to proceed to their final destinations. EDEM2 plays a critical role in this process by recognizing and eliminating misfolded glycoproteins. By targeting these aberrant proteins for degradation, EDEM2 helps maintain the overall integrity and functionality of the proteome.

Clinical Implications

Dysregulation of ERAD and protein quality control mechanisms can have severe consequences for cellular homeostasis. Mutations or deficiencies in EDEM2 have been associated with various diseases, including neurodegenerative disorders and metabolic disorders. Understanding the role of EDEM2 in protein quality control may provide insights into the pathogenesis of these diseases and potentially lead to the development of therapeutic interventions.