人类无脱模蛋白(ECD)的生物物理特性和建模支持脚手架功能。

IF 1.1 Q4 BIOPHYSICS
AIMS Biophysics Pub Date : 2016-01-01 Epub Date: 2016-03-09 DOI:10.3934/biophy.2016.1.195
Riyaz A Mir, Jeff Lovelace, Nicholas P Schafer, Peter D Simone, Admir Kellezi, Carol Kolar, Gaelle Spagnol, Paul L Sorgen, Hamid Band, Vimla Band, Gloria E O Borgstahl
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引用次数: 4

摘要

果蝇脱模蛋白(ECD)的人类同源物是一种p53结合蛋白,能够稳定和增强p53的功能。小鼠Ecd的纯合缺失是早期胚胎致死的,并且Ecd缺失会延迟G1-S细胞周期的进展。重要的是,ECD直接与Rb肿瘤抑制因子相互作用,并与E2F转录因子竞争与Rb结合。进一步的研究表明,ECD在乳腺癌和胰腺癌中过度表达,其过度表达与患者生存不良相关。ECD过表达与Ras通过上调自噬诱导细胞转化。最近,我们证明了CK2介导的ECD磷酸化和与R2TP复合物的相互作用对其细胞周期调节功能很重要。考虑到ECD是多蛋白复合物的组成部分,其晶体结构未知,我们通过圆二色性测量和序列分析软件对ECD结构进行了表征。这些分析表明,大部分ECD是由α-螺旋组成的。此外,小角x射线散射(SAXS)分析表明,缺失片段ECD(1-432)和ECD(1-534)折叠良好,显示前400个残基呈球形,后100个残基呈扩展柱状结构。综合所有这些结果,我们推测ECD在与其蛋白伙伴的关联中起着结构枢纽或支架蛋白的作用。在未来,这里提出的假设ECD模型将需要进行实验测试。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biophysical characterization and modeling of human Ecdysoneless (ECD) protein supports a scaffolding function.

Biophysical characterization and modeling of human Ecdysoneless (ECD) protein supports a scaffolding function.

Biophysical characterization and modeling of human Ecdysoneless (ECD) protein supports a scaffolding function.

Biophysical characterization and modeling of human Ecdysoneless (ECD) protein supports a scaffolding function.

The human homolog of Drosophila ecdysoneless protein (ECD) is a p53 binding protein that stabilizes and enhances p53 functions. Homozygous deletion of mouse Ecd is early embryonic lethal and Ecd deletion delays G1-S cell cycle progression. Importantly, ECD directly interacts with the Rb tumor suppressor and competes with the E2F transcription factor for binding to Rb. Further studies demonstrated ECD is overexpressed in breast and pancreatic cancers and its overexpression correlates with poor patient survival. ECD overexpression together with Ras induces cellular transformation through upregulation of autophagy. Recently we demonstrated that CK2 mediated phosphorylation of ECD and interaction with R2TP complex are important for its cell cycle regulatory function. Considering that ECD is a component of multiprotein complexes and its crystal structure is unknown, we characterized ECD structure by circular dichroism measurements and sequence analysis software. These analyses suggest that the majority of ECD is composed of α-helices. Furthermore, small angle X-ray scattering (SAXS) analysis showed that deletion fragments, ECD(1-432) and ECD(1-534), are both well-folded and reveals that the first 400 residues are globular and the next 100 residues are in an extended cylindrical structure. Taking all these results together, we speculate that ECD acts like a structural hub or scaffolding protein in its association with its protein partners. In the future, the hypothetical model presented here for ECD will need to be tested experimentally.

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来源期刊
AIMS Biophysics
AIMS Biophysics BIOPHYSICS-
CiteScore
2.40
自引率
20.00%
发文量
16
审稿时长
8 weeks
期刊介绍: AIMS Biophysics is an international Open Access journal devoted to publishing peer-reviewed, high quality, original papers in the field of biophysics. We publish the following article types: original research articles, reviews, editorials, letters, and conference reports. AIMS Biophysics welcomes, but not limited to, the papers from the following topics: · Structural biology · Biophysical technology · Bioenergetics · Membrane biophysics · Cellular Biophysics · Electrophysiology · Neuro-Biophysics · Biomechanics · Systems biology
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