Slp1-Emp65: A Guardian Factor that Protects Folding Polypeptides from Promiscuous Degradation

Area of Science:

• Cell Biology
• Molecular Biology
• Protein Homeostasis (Proteostasis)

Background:

• Newly synthesized proteins rely on molecular chaperones for proper folding.
• Cellular quality control systems target misfolded proteins for degradation.
• Chaperones paradoxically can also target unfolded proteins for degradation, posing a risk to nascent polypeptides.

Purpose of the Study:

• To identify the mechanism that prevents the degradation of actively folding polypeptides.
• To characterize the function of the Slp1-Emp65 complex in the endoplasmic reticulum.

Main Methods:

• Investigated the role of the Slp1-Emp65 complex in protein folding and degradation.
• Assessed the impact of the Slp1-Emp65 complex absence on newly synthesized protein fate.

Main Results:

• Identified a conserved endoplasmic reticulum (ER) membrane protein complex (Slp1-Emp65) that binds unfolded proteins.
• Demonstrated that the Slp1-Emp65 complex protects soluble proteins from degradation during the folding process.
• Showed that in the absence of the Slp1-Emp65 complex, 20%-30% of potentially foldable proteins are degraded.

Conclusions:

• The Slp1-Emp65 complex functions as a crucial protector of newly synthesized, actively folding proteins.
• Discovered a new class of proteostasis factors termed "guardian" proteins.
• Highlighted the vulnerability of nascent polypeptides and the importance of dedicated protective mechanisms.