Conformational changes of purine repressor DNA-binding domain upon complexation with DNA

Area of Science:

• Structural biology
• Molecular biology
• Biochemistry

Background:

• The purine repressor (PurR) has two domains: DNA-binding and corepressor-binding.
• Previous studies determined the PurR-corepressor-operator complex structure via X-ray crystallography.

Purpose of the Study:

• To determine the solution structure of the PurR DNA-binding domain in its DNA-free state.
• To compare the DNA-free structure with the DNA-bound structure.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the solution structure.
• X-ray crystallography was used for the DNA-bound structure.

Main Results:

• The DNA-free PurR DNA-binding domain consists of three helices, with the fourth helix (hinge helix) being disordered.
• The first three helices maintain a similar architecture in both DNA-free and DNA-bound states.
• Specific DNA binding and corepressor-induced dimerization trigger the hinge helix formation.

Conclusions:

• The PurR DNA-binding domain undergoes conformational changes upon DNA binding and dimerization.
• The hinge helix is an intrinsically disordered region in the absence of DNA and dimerization.
• Understanding these structural dynamics is crucial for purine metabolism regulation.