Phase separation of protein kinase A regulatory subunits is driven by similar inter- and intra-molecular interactions involving the inhibitory segment

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Phase separation of protein kinase A regulatory subunits is driven by similar inter- and intra-molecular interactions involving the inhibitory segment

bioRxiv (preprint) 2025
Malyasree Giri, Christopher S. Brasnett, Kübra F. Eroglu, Julie Maibøll Kaasen, Alain A.M. Andre, Siewert-Jan Marrink, Frans A.A. Mulder, Magnus Kjaergaard

Using NMR spectroscopy and molecular dynamics simulations, researchers show that phase separation of the PKA regulatory subunit RIα is driven by arginine residues in its inhibitory segment, which engage in similar inter- and intra-molecular interactions with the folded dimerization/docking domain. Flow Induced Dispersion Analysis (FIDA), on a Fida 1 instrument, was used to measure the hydrodynamic radii of two RIα constructs in solution, corroborating dynamic light scattering results and confirming the expected size increase from the added disordered inhibitory-segment region. It is an example of using FIDA to characterize the size and hydrodynamic properties of intrinsically disordered protein constructs in free solution.

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Phase separation of protein kinase A regulatory subunits is driven by similar inter- and intra-molecular interactions involving the inhibitory segment
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