6ES6

Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins

6ES6 の概要

• エントリーDOI: 10.2210/pdb6es6/pdb
• NMR情報: BMRB: 34188
• 分子名称: CID, NCBD (2 entities in total)
• 機能のキーワード: ncbd, cid, complex, idp, dna binding protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 10417.65

構造登録者

Chi, N.C. (登録日: 2017-10-19, 公開日: 2018-10-31, 最終更新日: 2024-05-15)

主引用文献

Jemth, P.,Karlsson, E.,Vogeli, B.,Guzovsky, B.,Andersson, E.,Hultqvist, G.,Dogan, J.,Guntert, P.,Riek, R.,Chi, C.N.
Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins.
Sci Adv, 4:eaau4130-eaau4130, 2018

PubMed Abstract: 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.

PubMed: 30397651
DOI: 10.1126/sciadv.aau4130

実験手法

SOLUTION NMR