Valérie GABELICA

MASS SPECTROMETRY FOR BIOPHYSICS: ASSEMBLY AND INTERACTIONS IN UNUSUAL DNA STRUCTURES

Valérie GABELICA
ARNA Laboratory (INSERM, CNRS & Université de Bordeaux), Institut Européen de Chimie et Biologie (IECB), Pessac, France

 Our team focuses on the measurement sciences and in particular, mass spectrometry, applied to study non-covalent interactions. Nucleic acids (and more recently, foldamers and protein therapeutics) are both our model systems1 and systems on which we learn new things. In the past years, we mainly studied G-quadruplex interactions with cations and ligands. By integrating mass spectrometry in the panel of biophysical methods, we have the advantage of a direct readout of the stoichiometry the complexes, and thus the ability to reveal unexpected ones. Recently we monitored the thermal denaturation of ligand-nucleic acid complexes by mass spectrometry.2 We revealed unexpected intermediate states, and characterized their thermodynamic parameters. Our results revisit years or biophysical research based on thermal denaturation. We also focus on developing new methods (from new hardware to novel concepts for data interpretation) to obtain additional structural information on each stoichiometry separated by mass spectrometry. These advanced methods coupled to MS are ion mobility spectrometry3 and ion spectroscopy. 1) Porrini M, Rosu F, Rabin C, Darré L, Gómez H, Orozco M, Gabelica V, Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry, ACS Cent. Sci. (2017) 3(5):454-461. 2) Marchand A, Rosu F, Zenobi R, Gabelica V, Thermal Denaturation of DNA G-Quadruplexes and their Complexes with Ligands: Thermodynamic Analysis of the Multiple States Revealed by Native Mass Spectrometry, J. Am. Chem. Soc. (2018), in press. DOI: 10.1021/jacs.8b07302. 3) Gabelica V, Marklund E. Fundamentals of ion mobility spectrometry, Curr. Opin. Chem. Biol. (2018) 42:51-59.