A ribosome-associating factor chaperones tail-anchored membrane proteins

Area of Science:

• Cell Biology
• Protein Targeting
• Membrane Biology

Background:

• Tail-anchored (TA) proteins insert into the endoplasmic reticulum (ER) membrane via a single C-terminal transmembrane domain (TMD).
• Cytosolic chaperones, like TRC40, are essential for targeting these hydrophobic TA proteins to the ER, preventing aggregation.
• The precise mechanism by which TRC40 efficiently captures TA proteins in the crowded cytosol remains unclear.

Purpose of the Study:

• To elucidate the mechanism of TA protein capture and targeting to the ER.
• To identify factors involved in facilitating TRC40's interaction with TA proteins.

Main Methods:

• Biochemical assays to identify protein complexes.
• Ribosome profiling to study protein synthesis and targeting.
• Depletion studies to assess the role of identified complexes in TA protein localization.

Main Results:

• A conserved three-protein complex (Bat3, TRC35, Ubl4A) was identified.
• This Bat3 complex is recruited to ribosomes and interacts with newly synthesized TA protein TMDs.
• The Bat3 complex transfers TA proteins to TRC40 for subsequent ER insertion.
• Depletion of the Bat3 complex leads to TA protein mislocalization, mediated by non-TRC40 factors.

Conclusions:

• The Bat3 complex functions as a TMD-selective chaperone for TA proteins.
• It facilitates efficient channeling of TA proteins to the TRC40 insertion pathway.
• This mechanism ensures accurate TA protein targeting and prevents mislocalization.