Signal-sequence induced conformational changes in the signal recognition particle

Area of Science:

• Molecular Biology
• Structural Biology
• Cell Biology

Background:

• Co-translational protein targeting is crucial for cellular membrane protein insertion.
• The signal recognition particle (SRP) pathway mediates this process, involving SRP, its receptor, and nascent proteins.
• Understanding the structural dynamics of SRP is key to elucidating protein targeting mechanisms.

Purpose of the Study:

• To elucidate the structural mechanism of signal sequence recognition and communication within SRP.
• To provide high-resolution crystal structures of SRP in both unbound and signal sequence-bound states.

Main Methods:

• X-ray crystallography was employed to determine the structures of unbound and signal sequence-bound SRP.
• Analysis of structural changes upon signal sequence binding was performed.

Main Results:

• The 2.9 Å crystal structures of unbound and signal sequence-bound SRP were determined.
• Signal sequence binding induces concerted folding of the GM linker helix, finger loop, and C-terminal alpha helix αM6.
• This coupled binding and folding mechanism allows for structural adaptability and repositioning of the NG domain.

Conclusions:

• SRP utilizes a coupled binding and folding mechanism for signal sequence recognition.
• This mechanism facilitates communication between the M and NG domains of SRP54, essential for receptor interaction.
• The findings provide insights into the allosteric regulation of co-translational protein targeting.