Native mass spectrometry is a widely used tool in structural biology, providing information on protein structure and interactions through preservation of complexes in the gas phase. Herein, the importance of intramolecular non‐covalent interactions in the gas phase has been studied by alanine scanning and collision‐induced unfolding (CIU) ion mobility‐mass spectrometry. Mutation of specific polar and ionic residues on the surface of an acyl carrier protein (ACP) were found to destabilise the compact gas‐phase structure with mutants E31A, D32A, D41A and D65A being particularly destabilised. Molecular dynamics simulations of the ACP 7+ and 8+ ions showed extended intramolecular interactions, resulting from sidechain collapse of polar surface residues, which were confined to the gas phase and consistent with the CIU data. These findings provide evidence for the importance of specific ionic residues, and their interactions, in the maintenance of compact protein gas‐phase structure.

The Front Cover shows collision‐induced unfolding (CIU) of an acyl carrier protein in the gas phase as measured by ion mobility spectrometry. The background shows a representation of the alanine scanning mutagenesis used to probe the importance of individual residues in stabilising the compact form of the protein. More information can be found in the Full Paper by J. Bellamy‐Carter, N. J. Oldham, and co‐workers.

Invited for this month's cover are the collaborating groups of Professor Neil Oldham at the University of Nottingham and Dr. Matthew Jenner at the University of Warwick, UK. The cover picture shows collision induced unfolding (CIU) of an acyl carrier protein in the gas‐phase as measured by ion mobility spectrometry. The background shows a representation of the alanine scanning mutagenesis used to probe the importance of individual residues in stabilising the compact form of the protein. Read the full text of the article at 10.1002/anse.202000019.