EWS-RNA结合蛋白1：通过构象动力学研究对尤因肉瘤的结构洞察

EWS-RNA Binding Protein 1: Structural Insights into Ewing Sarcoma by Conformational Dynamics Investigations.

作者信息

Shahzadi Saba, Yasir Muhammad, Kloczkowski Andrzej, Hassan Mubashir

机构信息

The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.

Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, 24341, Republic of Korea.

出版信息

Curr Cancer Drug Targets. 2025 Mar 11. doi: 10.2174/0115680096330765250220053705.

DOI:10.2174/0115680096330765250220053705

PMID:40070334

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12292270/

Abstract

BACKGROUND

Prior research has demonstrated that proteins play a significant role in the prognosis and treatments of various sarcomas, including Ewing sarcoma through the interplay of downstream signaling cascades. However, there is limited understanding about the strcucture conformation of EWSR1 and its structural implication in the prognosis of Ews-ing Sarcoma by interaction with RNA molecules.

AIMS

The primary goal of ongoing research is to determine how EWSR1 contributes to Ewing sarcoma.

OBJECTIVE

The current study explores the complexity of EWSR1 structure and its conforma-tional interactions with RNA in relation to Ewing sarcoma.

METHODS

Here, we employed a comparative modeling approach to predict EWSR1 domains separately and assembled them into one structural unit using a DEMO server. Additionally, the RNA motifs interacting with EWSR1 were predicted, and the 3D model was built using RNAComposer. Protein-RNA docking and MD simulation studies were carried out to check the intermolecular interactions and stability behavior of docked EWSR1-RNA complexes.

RESULTS

The overall results explore the structural insights into EWSR1 and their interactions with RNA, which may play a momentous role in co- and post-transcriptional regulation to control gene expression.

CONCLUSION

Taken togather, our findings suggest that EWSR1 may be a useful therapeutic target for the diagnosis and management of Ewing sarcoma.

摘要

背景

先前的研究表明，蛋白质在包括尤因肉瘤在内的各种肉瘤的预后和治疗中发挥着重要作用，其通过下游信号级联的相互作用来实现。然而，对于EWSR1的结构构象及其与RNA分子相互作用在尤因肉瘤预后中的结构影响，人们的了解有限。

目的

正在进行的研究的主要目标是确定EWSR1如何促成尤因肉瘤。

目的

当前的研究探讨了EWSR1结构的复杂性及其与尤因肉瘤相关的RNA的构象相互作用。

方法

在这里，我们采用比较建模方法分别预测EWSR1结构域，并使用DEMO服务器将它们组装成一个结构单元。此外，预测了与EWSR1相互作用的RNA基序，并使用RNAComposer构建了三维模型。进行了蛋白质-RNA对接和分子动力学模拟研究，以检查对接的EWSR1-RNA复合物的分子间相互作用和稳定性行为。