Solution and Gas-Phase Stability of DNA Junctions from Temperature-Controlled Electrospray Ionization and Surface-Induced Dissociation

被引:8
作者
Pruska, Adam [1 ]
Harrison, Julian A. [1 ]
Granzhan, Anton [2 ]
Marchand, Adrien [1 ]
Zenobi, Renato [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland
[2] Paris Saclay Univ, Inst Curie, CNRS, INSERM,U1196,UMR9187, F-91405 Orsay, France
基金
瑞士国家科学基金会;
关键词
MASS-SPECTROMETRY; 3-WAY JUNCTIONS; G-QUADRUPLEXES; WEB SERVER; PROTEIN; BINDING; COMPLEXES; DUPLEXES; DAMAGE; DOMAIN;
D O I
10.1021/acs.analchem.3c02742
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
DNA three-way junction (TWJ) structures transiently form during key cellular processes such as transcription, replication, and DNA repair. Despite their significance, the thermodynamics of TWJs, including the influence of strand length, base pair composition, and ligand binding on TWJ stability and dissociation mechanisms, are poorly understood. To address these questions, we interfaced temperature-controlled nanoelectrospray ionization mass spectrometry (TC-nESI-MS) with a cyclic ion mobility spectrometry (cIMS) instrument that was also equipped with a surface-induced dissociation (SID) stage. This novel combination allowed us to investigate the structural intermediates of three TWJ complexes and examine the effects of GC base pairs on their dissociation pathways. We found that two TWJ-specific ligands, 2,7-tris-naphthalene (2,7-TrisNP) and tris-phenoxybenzene (TrisPOB), lead to TWJ stabilization, revealed by an increase in the melting temperature (T-m) by 13 or 26 degrees C, respectively. To gain insights into conformational changes in the gas phase, we employed cIMS and SID to analyze TWJs and their complexes with ligands. Analysis of IM arrival distributions suggested a single-step dissociation of TWJs and their intermediates for the three studied TWJ complexes. Upon ligand binding, a higher SID energy by 3 V (2,7-TrisNP) and 5 V (TrisPOB) was required to induce 50% dissociation of TWJ, compared to 38 V in the absence of ligands. Our results demonstrate the power of utilizing TC-nESI-MS in combination with cIMS and SID for thermodynamic characterization of TWJ complexes and investigation of ligand binding. These techniques are essential for the TWJ design and development as drug targets, aptamers, and structural units for functional biomaterials.
引用
收藏
页码:14384 / 14391
页数:8
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