Heterodimeric GTPase core of the SRP targeting complex

Area of Science:

• Molecular biology
• Structural biology
• Biochemistry

Background:

• Protein targeting to cellular membranes is crucial for cellular function.
• Signal recognition particle (SRP) pathway mediates cotranslational protein targeting.
• GTPases Ffh and FtsY are key components of the SRP pathway.

Purpose of the Study:

• To elucidate the structural basis of the interaction between Ffh and FtsY GTPase domains.
• To understand the mechanism of coordinate activation of these GTPases.
• To investigate how this complex signals to other components of the protein targeting machinery.

Main Methods:

• X-ray crystallography at 2.05 angstrom resolution.
• Structural analysis of the Ffh-FtsY GTPase domain complex.
• Biochemical assays to study GTPase activity and nucleotide binding.

Main Results:

• A remarkably symmetric heterodimer of Ffh and FtsY NG GTPase domains was resolved.
• The heterodimer sequesters a composite active site with two bound nucleotides.
• The structure explains the coordinated activation of both GTPases.
• Extensive interface formation suggests allosteric signaling mechanisms.

Conclusions:

• The Ffh-FtsY heterodimer acts as a molecular latch, regulating protein targeting.
• Complex formation and GTPase active site assembly are critical for regulating the latch.
• This structural insight provides a framework for understanding SRP-mediated protein translocation.