溶液中ATAD2溴结构域聚集行为的研究

doi:10.11938/cjmr20222993

波谱学杂志 ›› 2023, Vol. 40 ›› Issue (2): 169-178.doi: 10.11938/cjmr20222993

溶液中ATAD2溴结构域聚集行为的研究

王远方^1,²,王小花^1,²,舒畅^1,²,张许^1,^2,^3,⁴,刘买利^1,^2,^3,⁴,曾丹云^1,^2,^*()

1.波谱与原子分子物理国家重点实验室，武汉磁共振中心，中国科学院精密测量科学与技术创新研究院，湖北武汉 430071
2.中国科学院大学，北京 100049
3.华中科技大学武汉光电国家研究中心，湖北武汉 430074
4.湖北光谷实验室，湖北武汉 430074

收稿日期:2022-04-06 出版日期:2023-06-05 在线发表日期:2022-05-30
通讯作者: 曾丹云 E-mail:zengdanyun@apm.ac.cn
基金资助:
国家重点基础研究发展计划（“973”计划）资助项目(2017YFA0505400);国家重点基础研究发展计划（“973”计划）资助项目(2018YFE0202300);国家重点基础研究发展计划（“973”计划）资助项目(2018YFA0704002)

The Aggregation of ATAD2 Bromodomain in Solution

WANG Yuanfang^1,²,WANG Xiaohua^1,²,SHU Chang^1,²,ZHANG Xu^1,^2,^3,⁴,LIU Maili^1,^2,^3,⁴,ZENG Danyun^1,^2,^*()

1. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China
2. University of Chinese Academy of Sciences, Beijing 100049, China
3. Wuhan National Research Center for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China
4. Optics Valley Laboratory, Wuhan 430074, China

Received:2022-04-06 Published:2023-06-05 Online:2022-05-30
Contact: ZENG Danyun E-mail:zengdanyun@apm.ac.cn

1. 附件材料.pdf(404KB)

摘要/Abstract

摘要：

三磷酸腺苷酶家族蛋白2（ATAD2）是一种染色质调节因子. 它的异常表达与多种恶性肿瘤的发生和发展密切相关，因此还被称为致癌转录辅助因子. ATAD2由ATP酶结构域和溴结构域组成. 其中，溴结构域可以特异性识别并结合组蛋白末端的乙酰化赖氨酸位点，调控染色体重构和转录，但其功能相关的很多结构特征并未可知. 我们首先发现ATAD2溴结构域在溶液中易发生聚集. 然后以核磁共振（NMR）和圆二色谱（CD）为主要研究手段，从环境因素和结构因素两方面对ATAD2溴结构域的聚集机理进行了初步探讨，发现该聚集行为伴有结构变化，并可能与功能相关. 本研究可能为ATAD2溴结构域抑制剂的研发提供新的思路.

关键词: 核磁共振（NMR）, ATAD2, 溴结构域, 聚集

Abstract:

ATPase family AAA domain-containing protein 2 (ATAD2) is a chromatin regulator, also known as an oncogenic transcription cofactor. Its abnormal expression is closely related to the occurrence and development of various malignant tumors. ATAD2 consists of two domains: the ATPase domain and the bromodomain. The bromodomain can specifically recognize and interact with the acetylated lysines in proteins, which regulates the refactoring and transcription of chromosomes. In this work, we found that ATAD2 bromodomains are aggregated under normal solution conditions. Considering the possible impact of aggregation on the interaction between ATAD2 bromodomain and acetylated histone tail, we preliminarily investigated the aggregation of ATAD2 bromodomains mainly by nuclear magnetic resonance (NMR) and circular dichroism (CD) spectra. The results suggested that the aggregation is accompanied with structure alteration and possibly related to the physiological functions of cells. This study may provide new clues for the development of ATAD2 bromodomain inhibitors.

Key words: nuclear magnetic resonance (NMR), ATAD2, bromodomain, aggregation

中图分类号:

O482.53

王远方,王小花,舒畅,张许,刘买利,曾丹云. 溶液中ATAD2溴结构域聚集行为的研究[J]. 波谱学杂志, 2023, 40(2): 169-178.

WANG Yuanfang,WANG Xiaohua,SHU Chang,ZHANG Xu,LIU Maili,ZENG Danyun. The Aggregation of ATAD2 Bromodomain in Solution[J]. Chinese Journal of Magnetic Resonance, 2023, 40(2): 169-178.

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参考文献 22

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溶液中ATAD2溴结构域聚集行为的研究

The Aggregation of ATAD2 Bromodomain in Solution

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