title: Emergence and evolution of an interaction between intrinsically disordered proteins.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Greta
authors.identifier: http://orcid.org/0000-0002-4136-6792
authors.initials: G
authors.lastname: Hultqvist
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Åberg
authors.affiliation: 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.
authors.forename: Carlo
authors.initials: C
authors.lastname: Camilloni
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Gustav N
authors.initials: GN
authors.lastname: Sundell
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Andersson
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.|Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Dogan
authors.affiliation: Laboratory of Physical Chemistry, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland.
authors.forename: Celestine N
authors.identifier: http://orcid.org/0000-0003-4154-2378
authors.initials: CN
authors.lastname: Chi
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Michele
authors.identifier: http://orcid.org/0000-0002-3616-1610
authors.initials: M
authors.lastname: Vendruscolo
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.identifier: http://orcid.org/0000-0003-1516-7228
authors.initials: P
authors.lastname: Jemth
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D000072417:Protein Domains; D060066:Protein Interaction Maps
chemical_list: D064267:Intrinsically Disordered Proteins
keywords: Affinity; Evolution; Protein-protein interaction; biophysics; computational biology; intrinsically disordered proteins; molecular dynamics; none; phylogenetic reconstruction; structural biology; systems biology