4UN2

Crystal structure of the UBA domain of Dsk2 in complex with Ubiquitin

4UN2 の概要

• エントリーDOI: 10.2210/pdb4un2/pdb
• 分子名称: UBIQUITIN, UBIQUITIN DOMAIN-CONTAINING PROTEIN DSK2 (3 entities in total)
• 機能のキーワード: protein binding, ubiquitin-associated domain, protein degradation
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Ubiquitin: Cytoplasm (By similarity): P0CG48; Nucleus (Probable): P48510
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13921.64

構造登録者

Michielssens, S.,Peters, J.H.,Ban, D.,Pratihar, S.,Seeliger, D.,Sharma, M.,Giller, K.,Sabo, T.M.,Becker, S.,Lee, D.,Griesinger, C.,de Groot, B.L. (登録日: 2014-05-23, 公開日: 2014-08-27, 最終更新日: 2024-01-10)

主引用文献

Michielssens, S.,Peters, J.H.,Ban, D.,Pratihar, S.,Seeliger, D.,Sharma, M.,Giller, K.,Sabo, T.M.,Becker, S.,Lee, D.,Griesinger, C.,De Groot, B.L.
A Designed Conformational Shift to Control Protein Binding Specificity.
Angew.Chem.Int.Ed.Engl., 53:10367-, 2014

PubMed Abstract: In a conformational selection scenario, manipulating the populations of binding-competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have a similar population in the wild-type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding-competent substates.

PubMed: 25115701
DOI: 10.1002/ANIE.201403102

実験手法

X-RAY DIFFRACTION (1.51 Å)