TY - JOUR TI - Emergence and evolution of an interaction between intrinsically disordered proteins AU - Hultqvist, Greta AU - Åberg, Emma AU - Camilloni, Carlo AU - Sundell, Gustav N AU - Andersson, Eva AU - Dogan, Jakob AU - Chi, Celestine N AU - Vendruscolo, Michele AU - Jemth, Per A2 - Kelly, Jeffery W VL - 6 PY - 2017 DA - 2017/04/11 SP - e16059 C1 - eLife 2017;6:e16059 DO - 10.7554/eLife.16059 UR - https://doi.org/10.7554/eLife.16059 AB - 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. KW - intrinsically disordered proteins KW - Evolution KW - Protein-protein interaction KW - Affinity KW - phylogenetic reconstruction KW - molecular dynamics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -