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Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.ORCID-id: 0000-0003-1516-7228
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
Univ Colorado Denver, Dept Biochem & Mol Genet, 12801 East 17th Ave, Aurora, CO 80045 USA.
Univ Buenos Aires, IQUIBICEN CONICET, FCEyN, Prot Physiol Lab, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina.
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2018 (engelsk)Inngår i: Science Advances, E-ISSN 2375-2548, Vol. 4, nr 10, artikkel-id eaau4130Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

In every established species, protein-protein interactions have evolved such that they are fit for purpose. However, the molecular details of the evolution of new protein-protein interactions are poorly understood. We have used nuclear magnetic resonance spectroscopy to investigate the changes in structure and dynamics during the evolution of a protein-protein interaction involving the intrinsically disordered CREBBP (CREB-binding protein) interaction domain (CID) and nuclear coactivator binding domain (NCBD) from the transcriptional coregulators NCOA (nuclear receptor coactivator) and CREBBP/p300, respectively. The most ancient low-affinity "Cambrian-like" [540 to 600 million years (Ma) ago] CID/NCBD complex contained less secondary structure and was more dynamic than the complexes from an evolutionarily younger "Ordovician-Silurian" fish ancestor (ca. 440 Ma ago) and extant human. The most ancient Cambrian-like CID/NCBD complex lacked one helix and several interdomain interactions, resulting in a larger solvent-accessible surface area. Furthermore, the most ancient complex had a high degree of millisecond-to-microsecond dynamics distributed along the entire sequences of both CID and NCBD. These motions were reduced in the Ordovician-Silurian CID/NCBD complex and further redistributed in the extant human CID/NCBD complex. Isothermal calorimetry experiments show that complex formation is enthalpically favorable and that affinity is modulated by a largely unfavorable entropic contribution to binding. Our data demonstrate how changes in structure and motion conspire to shape affinity during the evolution of a protein-protein complex and provide direct evidence for the role of structural, dynamic, and frustrational plasticity in the evolution of interactions between intrinsically disordered proteins.

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AMER ASSOC ADVANCEMENT SCIENCE , 2018. Vol. 4, nr 10, artikkel-id eaau4130
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URN: urn:nbn:se:uu:diva-369756DOI: 10.1126/sciadv.aau4130ISI: 000449221200069PubMedID: 30397651OAI: oai:DiVA.org:uu-369756DiVA, id: diva2:1271611
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Swedish Research CouncilTilgjengelig fra: 2018-12-17 Laget: 2018-12-17 Sist oppdatert: 2018-12-17bibliografisk kontrollert

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