Structure transformation of the tandem UIM in AT3 and their cooperative interactions with ubiquitin chains

The research team led by Prof. Hongyu Hu (SIBCB) recently achieved results on structure transformation of the tandem ubiquitin-interaction motif (UIM) in ataxin-3 (AT3) and their cooperative interactions with ubiquitin chains. Their findings were published in PLoS ONE on October, 7th.

 

UIM is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. In the study, the researchers elucidated the structures and dynamics of the tandem UIMs of AT3 (AT3-UIM12) both in free and Ub-bound forms. The solution structure of free AT3-UIM12 consists of two α-helices and a flexible linker, whereas that of the Ub-bound form is much more compact with hydrophobic contacts between the two helices. NMR dynamics indicates that the flexible linker becomes rigid when AT3-UIM12 binds with Ub. Isothermal titration calorimetry and NMR titration demonstrate that AT3-UIM12 binds diUb with two distinct affinities, and the linker plays a critical role in association of the two helices in diUb binding. These results provide an implication that the tandem UIM12 interacts with Ub or diUb in a cooperative manner through an allosteric effect and dynamics change of the linker region, which might be related to its recognitions with various Ub chains and ubiquitinated substrates.

 

This project was completed together with Prof. Donghai Lin from Shanghai Institute of Materia Medica.