Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains.
Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains.
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Ataxin-3 中串联泛素相互作用基序的结构转变及其与泛素链的协同相互作用。
DOI：
10.1371/journal.pone.0013202
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发表时间：
2010-10-07
期刊：
影响因子：
3.7
通讯作者：
Hu HY
中科院分区：
文献类型：
--
作者：
Song AX;Zhou CJ;Peng Y;Gao XC;Zhou ZR;Fu QS;Hong J;Lin DH;Hu HY
泛素相互作用基序(UIM)是一种具有结合泛素(Ub)和促进泛素化双重功能的短肽。我们阐明了ataxin-3串联UIMs(AT3-UIM12)在游离态和Ub结合态的结构和动力学。游离AT3-UIM12的溶液结构由两个α-螺旋和一个柔性连接子组成，而Ub结合形式的溶液结构更紧密，两个螺旋之间存在疏水接触。核磁共振动力学表明，当AT3-UIM12与Ub结合时，柔性连接体变得刚性。等温滴定热法和核磁共振滴定表明AT3-UIM12以两种不同的亲和力与diUb结合，连接子在diUb结合的两个螺旋的结合中起着关键作用。这些结果表明，串联的UIM12与Ub或diUb通过变构效应和连接区的动力学变化以协同的方式相互作用，这可能与其对不同Ub链和泛素化底物的识别有关。
The ubiquitin-interacting motif (UIM) is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. We elucidated the structures and dynamics of the tandem UIMs of ataxin-3 (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.
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