A signal sequence receptor in the endoplasmic reticulum membrane

Area of Science:

• Molecular Biology
• Cell Biology
• Protein Trafficking

Background:

• Protein translocation across the endoplasmic reticulum (ER) membrane is crucial for secretory pathway function.
• The signal sequence of nascent secretory proteins directs them to the ER.
• The signal recognition particle (SRP) initially binds to the signal sequence and nascent polypeptide.

Purpose of the Study:

• To investigate the fate of the signal sequence after SRP disengagement from the ribosome and ER membrane.
• To identify novel components involved in the post-SRP interaction with the signal sequence.

Main Methods:

• Crosslinking approach to study protein interactions.
• Investigation of nascent preprolactin signal sequence fate.
• Biochemical characterization of ER membrane proteins.

Main Results:

• The signal recognition particle (SRP) disengages from the ribosome and signal sequence upon attachment to the ER membrane via the SRP-receptor.
• A novel signal sequence receptor (SSR) was identified.
• The SSR is an integral, glycosylated rough ER membrane protein (Mr approximately 35K) that interacts with the signal sequence after SRP release.

Conclusions:

• The signal sequence interacts with a new receptor (SSR) on the ER membrane after SRP dissociation.
• This interaction is a key step in guiding the signal sequence and nascent polypeptide into the ER translocation channel.