Insights into High Affinity Small Ubiquitin-like Modifier (SUMO) Recognition by SUMO-interacting Motifs (SIMs) Revealed by a Combination of NMR and Peptide Array Analysis
Insights into High Affinity Small Ubiquitin-like Modifier (SUMO) Recognition by SUMO-interacting Motifs (SIMs) Revealed by a Combination of NMR and Peptide Array Analysis
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DOI：
10.1074/jbc.m111.293118
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发表时间：
2012-01-27
影响因子：
4.8
通讯作者：
Chen, Yuan
中科院分区：
文献类型：
--
作者：
Namanja, Andrew T.;Li, Yi-Jia;Chen, Yuan
小的泛素样修饰物(SUMO)调节许多基本的细胞功能。只有一种类型的相扑相互作用基序(SIM)可以将相扑的β-折叠延伸为平行或反平行的链。SIM结合方向和平行线特异性的分子决定因素尚不清楚。为了解决这个问题，我们利用核磁共振方法对SUMO1与SUMO1特异性SIM的复合体进行了结构研究，该SIM以高亲和力与SUMO1结合，而不需要翻译后修饰。此外，与另一种以相反方向结合的高亲和力SIM相比，多肽阵列已经研究了SIM序列要求。我们发现，反平行结合的SIMs可以容忍更多不同的序列，而平行结合的SIMS更喜欢由(I/V)DLT组成的更严格的序列，这些序列倾向于高亲和力的SUMO2和-3结合。对两个以相反方向结合的高亲和力SUMO1结合SIMs的比较揭示了高亲和力结合所需的共同的SUMO1特异性相互作用。这项研究极大地促进了我们对支持相扑-SIM识别的分子决定因素的理解。
The small ubiquitin-like modifiers (SUMOs) regulate many essential cellular functions. Only one type of SUMO-interacting motif (SIM) has been identified that can extend the beta-sheet of SUMO as either a parallel or an antiparallel strand. The molecular determinants of the bound orientation and paralogue specificity of a SIM are unclear. To address this question, we have conducted structural studies of SUMO1 in complex with a SUMO1-specific SIM that binds to SUMO1 with high affinity without post-translational modifications using nuclear magnetic resonance methods. In addition, the SIM sequence requirements have been investigated by peptide arrays in comparison with another high affinity SIM that binds in the opposing orientation. We found that antiparallel binding SIMs tolerate more diverse sequences, whereas the parallel binding SIMs prefer the more strict sequences consisting of (I/V) DLT that have a preference in high affinity SUMO2 and -3 binding. Comparison of two high affinity SUMO1-binding SIMs that bind in opposing orientations has revealed common SUMO1-specific interactions needed for high affinity binding. This study has significantly advanced our understanding of the molecular determinants underlining SUMO-SIM recognition.