Collision induced unfolding and dissociation differentiates ATP-competitive from allosteric protein tyrosine kinase inhibitors

VHH characterization.Recombinant VHHs: Production, characterization and affinity

“…However, this instrumental bottleneck can sometimes be circumvented by monitoring ion conformations from their native state(s) to their activated state(s) through a collision induced unfolding (CIU) step performed in the gas-phase [73]. Besides giving insights into ion conformational stability, this alternative can also help to resolve two undistinguishable native conformations evolving however towards IM-distinguishable conformational intermediates and has already been applied with success to various protein complexes [74][75][76]. Such studies are typically led by first submitting ions to growing collisional energies in the trap cell before separating them in the IM cell.…”

Structural O-Glycoform Heterogeneity of the SARS-CoV-2 Spike Protein Receptor-Binding Domain Revealed by Native Top-Down Mass Spectrometry

“…[40][41][42] In contrast, by combining glycoproteomics with the top-down MS approach, which preserves the intact glycoprotein enabling high-resolution proteoform-resolved analysis, [43][44][45] we could achieve the simultaneous characterization of the molecular structures, the site specificity, and the relative abundance of various glycoforms. Furthermore, by integrating native MS, which has recently emerged as a powerful structural biology tool to study protein structure-function relationships, [46][47][48][49][50][51][52] with trapped ion mobility spectrometry (TIMS), [53][54][55] we can investigate the gas phase structural variants to achieve the direct quantification of individual glycoproteoforms.…”

Experimental and theoretical investigation of overall energy deposition in surface-induced unfolding of protein ions

“…Native ion mobility-mass spectrometry (IM-MS), which can be used to characterize the overall shape and size of an ion by determining its collisional cross section (CCS) in a buffer gas, is a powerful tool for the investigation of high-order structure 1. Various gas-phase dissociation methods can be used to disrupt covalent and/or non-covalent interactions in order to probe structural characteristics such as sequence,2–4 location of ligand binding or post-translational modifications,3–5 connectivity of subunits in a complex,6–8 and differences in stability between closely-related structures 9,10. These dissociation methods vary as to how the ion is activated, i.e.…”