适体
小角X射线散射
指数富集配体系统进化
DNA
生物物理学
化学
分子动力学
计算生物学
结晶学
生物
生物化学
散射
核糖核酸
基因
分子生物学
计算化学
物理
光学
作者
Shigehiro Yamamoto,Fumiaki Kono,Kazuma Nakatani,Miwako Hirose,Katsunori Horii,Yoshitaka Hippo,Taro Tamada,Yusuke Suenaga,Tatsuhiro Matsuo
标识
DOI:10.3389/fonc.2023.1213678
摘要
NCYM, a Homininae-specific oncoprotein, is the first de novo gene product experimentally shown to have oncogenic functions. NCYM stabilizes MYCN and β-catenin via direct binding and inhibition of GSK3β and promotes cancer progression in various tumors. Thus, the identification of compounds that binds to NCYM and structural characterization of the complex of such compounds with NCYM are required to deepen our understanding of the molecular mechanism of NCYM function and eventually to develop anticancer drugs against NCYM. In this study, the DNA aptamer that specifically binds to NCYM and enhances interaction between NCYM and GSK3β were identified for the first time using systematic evolution of ligands by exponential enrichment (SELEX). The structural properties of the complex of the aptamer and NCYM were investigated using atomic force microscopy (AFM) in combination with truncation and mutation of DNA sequence, pointing to the regions on the aptamer required for NCYM binding. Further analysis was carried out by small-angle X-ray scattering (SAXS). Structural modeling based on SAXS data revealed that when isolated, NCYM shows high flexibility, though not as a random coil, while the DNA aptamer exists as a dimer in solution. In the complex state, models in which NCYM was bound to a region close to an edge of the aptamer reproduced the SAXS data. Therefore, using a combination of SELEX, AFM, and SAXS, the present study revealed the structural properties of NCYM in its functionally active form, thus providing useful information for the possible future design of novel anti-cancer drugs targeting NCYM.
科研通智能强力驱动
Strongly Powered by AbleSci AI