Deciphering of interactions between platinated DNA and HMGB1 by hydrogen/deuterium exchange mass spectrometry

doi:10.1039/c7dt00275k

CORC > 化学研究所 > 中国科学院化学研究所

	Deciphering of interactions between platinated DNA and HMGB1 by hydrogen/deuterium exchange mass spectrometry
	Wang, Yuanyuan 1,2; Du, Zhifeng 1,4; Zheng, Wei 1; Wu, Kui 1; Xu, Decheng 3; Luo, Qun 1; Zhao, Yao 1; Han, Juanjuan 1; Liu, Yangzhong 3; Wang, Fuyi 1,2
刊名	DALTON TRANSACTIONS
	2017-05-21
卷号	46 期号:19 页码:6187-6195
ISSN号	1477-9226
DOI	10.1039/c7dt00275k
英文摘要	A high mobility group box 1 (HMGB1) protein has been reported to recognize both 1,2-intrastrand crosslinked DNA by cisplatin (1,2-cis-Pt-DNA) and monofunctional platinated DNA using trans-[ PtCl2(NH3) (thiazole)] (1-trans-PtTz-DNA). However, the molecular basis of recognition between the trans-PtTz-DNA and HMGB1 remains unclear. In the present work, we described a hydrogen/deuterium exchange mass spectrometry (HDX-MS) method in combination with docking simulation to decipher the interactions of platinated DNA with domain A of HMGB1. The global deuterium uptake results indicated that 1-transPtTz-DNA bound to HMGB1a slightly tighter than the 1,2-cis-Pt-DNA. The local deuterium uptake at the peptide level revealed that the helices I and II, and loop 1 of HMGB1a were involved in the interactions with both platinated DNA adducts. However, docking simulation disclosed different H-bonding networks and distinct DNA-backbone orientations in the two Pt-DNA-HMGB1a complexes. Moreover, the Phe37 residue of HMGB1a was shown to play a key role in the recognition between HMGB1a and the platinated DNAs. In the cis-Pt-DNA-HMGB1a complex, the phenyl ring of Phe37 intercalates into a hydrophobic notch created by the two platinated guanines, while in the trans-PtTz-DNA-HMGB1a complex the phenyl ring appears to intercalate into a hydrophobic crevice formed by the platinated guanine and the opposite adenine in the complementary strand, forming a penta-layer p-p stacking associated with the adjacent thymine and the thiazole ligand. This work demonstrates that HDX-MS associated with docking simulation is a powerful tool to elucidate the interactions between platinated DNAs and proteins.
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000401526700008
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/44955]
专题	中国科学院化学研究所
通讯作者	Du, Zhifeng; Wang, Fuyi
作者单位	1.Chinese Acad Sci, Beijing Natl Lab Mol Sci, Natl Ctr Mass Spectrometry Beijing, CAS Key Lab Analyt Chem Living Biosyst,Inst Chem, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Univ Sci & Technol China, Dept Chem, Hefei 230026, Anhui, Peoples R China 4.Virginia Commonwealth Univ, Dept Chem, Box 2006, Richmond, VA 23284 USA
推荐引用方式 GB/T 7714	Wang, Yuanyuan,Du, Zhifeng,Zheng, Wei,et al. Deciphering of interactions between platinated DNA and HMGB1 by hydrogen/deuterium exchange mass spectrometry[J]. DALTON TRANSACTIONS,2017,46(19):6187-6195.
APA	Wang, Yuanyuan.,Du, Zhifeng.,Zheng, Wei.,Wu, Kui.,Xu, Decheng.,...&Wang, Fuyi.(2017).Deciphering of interactions between platinated DNA and HMGB1 by hydrogen/deuterium exchange mass spectrometry.DALTON TRANSACTIONS,46(19),6187-6195.
MLA	Wang, Yuanyuan,et al."Deciphering of interactions between platinated DNA and HMGB1 by hydrogen/deuterium exchange mass spectrometry".DALTON TRANSACTIONS 46.19(2017):6187-6195.