[Seminar] A journey into structural mass spectrometry methods

Title
A journey into structural mass spectrometry methods: from biotherapeutics to structural biology

Speaker
Sarah Cianferani
Diretora Científica e Investigadora Principal at BioOrganic Mass Spectrometry Laboratory in National Center for Scientific Research (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Strasbourg, França

Abstract

Structural mass spectrometry (MS) has emerged as a versatile and powerful tool for investigating the intricate structures of intact “nearly native” biological complexes and therapeutic proteins, effectively bridging the gap between molecular and structural characterization. This strategy encompasses a comprehensive set of MS-based methods, such as native MS, cross-linking, hydrogen-deuterium exchange, and top-down proteomics, with the primary goal of collecting extensive structural information on biomolecular complexes. By combining high resolution and sensitivity of MS with various biophysical and analytical techniques, structural MS enables the exploration of the three-dimensional architecture, conformational dynamics, and interactions of large biomolecules.

Until recently, these techniques were primarily the playground of a handful of experts. However, significant progress in sample preparation, MS instrumentation, and data analysis has sparked increasing interest in structural MS methods. It now overcomes challenges related to size, heterogeneity, and solubility of a wide range of protein complexes, and has integrated most structural biology programs. As crucial information regarding the higher-order structure, post-translational modifications, and heterogeneity of biologics can be obtained with structural MS, it has also made its way into the biopharmaceutical industry for the characterization of biologics, including therapeutic antibodies, recombinant proteins, and nucleic acid-based drugs.

Based on my personal journey into the structural MS field, I will present a panel of applications, ranging from the mutiprotein complexes in structural biology to therapeutic proteins.