Our study describes the structure of a protein complex involved in communication between neurons. Both interaction partners, the postsynaptic, intrinsically disordered scaffold protein GKAP and the so-called hub protein LC8, are bivalent, which in principle allows for the formation of a wide variety of complexes, much like building different structures from the same set of Lego bricks.

Our results show, however, that GKAP and LC8 form a single, well-defined complex with a specific stoichiometry and topology, in which two GKAP molecules are linked by LC8 dimers. Remarkably, despite this defined organization, the overall structure of the complex remains highly flexible and dynamic. It resembles a zipper on a sweater, providing a strong yet elastic connection.

In his Commentary, Prof. Elisar Barbar, an internationally recognized expert on LC8-mediated protein complexes, highlights several distinctive features of the system we studied that set it apart from previously characterized complexes, including its pronounced flexibility and specific atomic-level details of the molecular interactions.

We are delighted that our results published in The FEBS Journal have attracted such focused attention from the scientific community. We hope that our research, carried out in national and international collaboration, will contribute in the long term to a deeper understanding of the functioning of complex molecular systems, both in neuronal communication and more broadly.