MMS discovers how intrinsically disordered DNA damage suppressor protein Dsup protects DNA through intermolecular binding

Microfluidic Modulation Spectroscopy (MMS) was used to study how the intrinsically disordered DNA damage suppressor protein (Dsup) binds to and protects DNA from radiation damage. As part of a broader study combining multiple biophysical techniques, MMS provided direct insight into the structural changes associated with this interaction. The MMS results presented here show that when Dsup binds to double-stranded DNA, both molecules undergo conformational changes: the DNA exhibits reduced base pairing, indicating slight unwinding of the helix, while Dsup becomes more structured, with increased alpha-helical and turn content. These findings suggest a coupled binding mechanism that contributes to Dsup’s ability to protect DNA. Overall, this work demonstrates that MMS can serve as a powerful method for observing intermolecular binding between different biomolecules such as DNA and proteins within a single experiment.