Work

A Conformation-Specific Approach to Native Top-down Mass Spectrometry

Year: 2024

Type: article

Abstract: Native top-down mass spectrometry is a powerful approach for characterizing proteoforms and has recently been applied to provide similarly powerful insights into protein conformation. Current approaches, however, are limited such that structural insights can only be obtained for the entire conformational landscape in bulk or without any direct conformational measurement. We report a new ion-mobility-enabled method for performing native top-down MS in a conformation-specific manner. Our approach identified conformation-linked differences in backbone dissociation for the model protein calmodulin, which simultaneously informs upon proteoform variations and provides structural insights. We also illustrate that our method can be applied to protein-ligand complexes, either to identify components or to probe ligand-induced structural changes.

Source: Journal of the American Society for Mass Spectrometry

DOI: 10.1021/jasms.4c00361

Authors: Hannah M. Britt, Aisha Ben-Younis, Nathanael Page, Konstantinos Thalassinos

Institutions: Institute of Structural and Molecular Biology, University College London, LGC, Birkbeck, University of London

Language: English

Topic: Mass Spectrometry Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: Wellcome Trust