Structural Dynamic Heterogeneity of Polyubiquitin Subunits Affects Phosphorylation Susceptibility
Structural Dynamic Heterogeneity of Polyubiquitin Subunits Affects Phosphorylation Susceptibility
复制标题
多聚泛素亚基的结构动态异质性影响磷酸化敏感性
DOI：
10.1021/acs.biochem.0c00619
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发表时间：
2021
期刊：
影响因子：
2.9
通讯作者：
Sugase Kenji
中科院分区：
文献类型：
--
作者：
Morimoto Daichi;Walinda Erik;Takashima Shingo;Nishizawa Mayu;Iwai Kazuhiro;Shirakawa Masahiro;Sugase Kenji
多泛素是一种由泛素分子共价连接而成的多功能蛋白质标签。由于泛素折叠的高刚性，多泛素链中的泛素部分似乎在结构上彼此等价。因此，目前尚不清楚链中特定的泛素部分是如何被某些蛋白质优先识别的，例如PINK1。在这里，我们通过核磁共振波谱分析表明，K48连接的二泛素的两个泛素部分存在结构上的动态异质性。我们的分析捕捉到了亚基不对称的结构波动，这些结构波动与泛素中两个泛素部分的闭合到开放的转变没有直接关系。值得注意的是，这些新发现的异质结构波动可能与PINK1磷酸化敏感性的增加有关。再加上链中泛素部分之间的静态三级结构几乎没有差异的事实，观察到的亚基特异性结构波动可能是区分链中单个泛素部分的一个重要因素，从而有助于翻译后修饰的效率和特异性。
Polyubiquitin is a multifunctional protein tag formed by the covalent conjugation of ubiquitin molecules. Due to the high rigidity of the ubiquitin fold, the ubiquitin moieties in a polyubiquitin chain appear to be structurally equivalent to each other. It is therefore unclear how a specific ubiquitin moiety in a chain may be preferentially recognized by some proteins, such as the kinase PINK1. Here we show that there is structural dynamic heterogeneity in the two ubiquitin moieties of K48-linked diubiquitin by NMR spectroscopic analyses. Our analyses capture subunit-asymmetric structural fluctuations that are not directly related to the closed-to-open transition of the two ubiquitin moieties in diubiquitin. Strikingly, these newly identified heterogeneous structural fluctuations may be linked to an increase in susceptibility to phosphorylation by PINK1. Coupled with the fact that there are almost no differences in static tertiary structure among ubiquitin moieties in a chain, the observed subunit-specific structural fluctuations may be an important factor that distinguishes individual ubiquitin moieties in a chain, thereby aiding both efficiency and specificity in post-translational modifications.