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Identification of a factor that accelerates substrate release from the signal recognition particle
Huping Wang1, Ramanujan S Hegde1
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Science (New York, N.Y.)
|November 28, 2024
Summary
TMEM208 accelerates the release of proteins from the signal recognition particle (SRP) at the endoplasmic reticulum (ER). This prevents errors in protein biogenesis, particularly for membrane proteins, maintaining cellular protein homeostasis.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Biogenesis
Background:
- The signal recognition particle (SRP) targets secretory and membrane proteins to the endoplasmic reticulum (ER).
- The mechanism of substrate release from SRP to translocation factors at the ER remains unclear.
Purpose of the Study:
- To investigate the role of TMEM208 in the release of SRP-bound cargo.
- To understand how TMEM208 influences protein biogenesis at the ER.
Main Methods:
- Investigated the interaction between TMEM208 and the SRP.
- Analyzed the impact of TMEM208 deficiency on protein insertion and biogenesis.
Main Results:
- TMEM208 binds to the SRP substrate binding domain, promoting cargo release.
- Loss of TMEM208 leads to delayed translocation initiation and impaired biogenesis of multipass membrane proteins.
- This delay causes excessive polypeptide synthesis before translocation engagement.
Conclusions:
- TMEM208 is crucial for efficient cargo handover from SRP to translocation machinery.
- TMEM208 facilitates prompt protein targeting, preventing biogenesis errors and maintaining protein homeostasis.
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