4.7 Article

The allosteric effect of the upper half of SENP1 contributes to its substrate selectivity for SUMO1 over SUMO2

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2023.2166997

关键词

SENP1; SUMO; molecular dynamics simulations; principal component analysis; allosteric communication; allostery

向作者/读者索取更多资源

Molecular dynamics simulations were performed to investigate the conformational dynamics of SENP1-SUMO1, SENP1-SUMO2, and apo SENP1 systems. Stronger interactions between SENP1 and SUMO1 were observed, which may explain the preference of SENP1 for processing SUMO1 over SUMO2. An allosteric propagation model was proposed to explain the substrate discrimination of SENP1.
SUMOylation regulates various cellular process and SENP1 (SUMO-specific protease 1) serves as a SUMO (small ubiquitin-related modifier) specific protease that participates in the SUMO cycle. Given its extensive influences on metabolic activities, SENP1 has gained more and more attentions in clinical treatments. However, there remains a question on why does the SENP1 prefer to process SUMO1 rather than SUMO2. Here, we performed molecular dynamics simulations of SENP1-SUMO1, SENP1-SUMO2, and apo SENP1 systems and observed distinct conformational dynamics in the upper half of the clamp and the three loops in the catalytic center of the SENP1. Principal component analysis revealed that the most prominent canonical variable represented the spatial distribution of the upper half of the clamp, while the openness of the cleft was closely related to the catalytic ability of SENP1. Further analysis of the SENP1-SUMO interactions revealed that the extensive and strong interactions between the SENP1 and SUMO1 were both in the interface of the upper half region and the catalytic center. Dynamic cross-correlation matrix analysis demonstrated that the inter-residue correlations in the SUMO1 system was much stronger, especially in the two essential regions belonging to the upper and lower half of cleft. Based on these observations, we proposed an allosteric propagation model and further testified it using the community analysis. These results revealed the propagation pathway of allosteric communication that contributed to the substrate discrimination of SENP1 upon SUMO1 and SUMO2.Communicated by Ramaswamy H. Sarma

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据