PhD defence by Freia Stryhn Buus

Charge-driven Interactions of Highly Charged Intrinsically Disordered Proteins: From Dimers to Condensates

Assessment Committee:
Associate Professor Petur O. Heidarsson, Department of Biology, University of Copenhagen (Chairperson)
Associate Professor Katherine Stott, University of Oxford
Associate Professor Anders Malmendal, Roskilde Universit

Supervisor(s):
Professor Birthe Brandt Kragelund

Department:
Department of Biology

Place:
Building 1, Room: Seminar room 1.2.03, Ole Maaløes Vej 5, 2200 København N

Email address to gain access to the thesis: freia.buus@bio.ku.dk 
You will either receive a copy of the thesis or be informed where you can read a physical copy.

Short description of the thesis:
Intrinsically disordered proteins (IDPs) often contain many charged residues, enabling electrostatic interactions that can give rise to high-affinity complexes while remaining dynamic and disordered. This thesis investigated how charge governs such interactions using linker histone H1.0 (H1) and prothymosin α (ProTα) as a model system. Residue-level studies showed that both proteins remain disordered within biomolecular condensates, although dynamics are reduced and K+ ions are preferentially excluded. Interactions between negatively charged ProTα and the positively charged folded domain H1-GD formed dynamic complexes without stable residue-specific contacts. Binding affinity depended on both net charge and charge clustering. Finally, H1-GD was shown to enhance CCR7-mediated chemokine signaling and chemotaxis through electrostatic interactions with the receptor’s negatively charged N-terminal region.