Switch-like compaction of poly(ADP-ribose) upon cation binding

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Poly(ADP-ribose) (PAR) is a posttranslational modification regulating cellular processes.
• PAR acts as a scaffold in macromolecular complexes and biomolecular condensates.
• The mechanism of PAR's specific molecular recognition remains unclear.

Purpose of the Study:

• To investigate the flexibility of PAR under varying cation conditions.
• To understand how cations influence PAR structure and compaction.
• To elucidate the role of PAR stiffness in molecular recognition.

Main Methods:

• Single-molecule fluorescence resonance energy transfer (smFRET) was employed.
• PAR flexibility was evaluated across different cation concentrations and valencies (Na+, Mg2+, Ca2+, spermine4+).
• The effect of the intrinsically disordered protein FUS on PAR compaction was assessed.

Main Results:

• PAR exhibits a longer persistence length compared to RNA and DNA.
• PAR undergoes a sharp transition from extended to compact states upon cation binding.
• The degree of PAR compaction is dependent on cation concentration and valency.
• The protein FUS also induced PAR compaction, acting as a macromolecular cation.

Conclusions:

• PAR molecules possess inherent stiffness.
• Cation binding triggers switch-like compaction of PAR.
• The cationic environment is a key factor driving PAR recognition specificity.