Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Emma Åberg
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Carlo Camilloni
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom; Department of Chemistry, Technische Universität München, München, Germany; Institute for Advanced Study, Technische Universität München, München, Germany
Gustav N Sundell
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Eva Andersson
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Jakob Dogan
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450–600 million years ago, while NCBD was present in the protostome/deuterostome ancestor. The most ancient CID/NCBD formed a relatively weak complex (Kd∼5 µM). At the time of the first vertebrate-specific whole genome duplication, the affinity had increased (Kd∼200 nM) and was maintained in further speciation. Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low-affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations.
