Structural Mass Spectrometry and Protein Misfolding
Recent news and developments from the lab.
We describe the development of DSSO-carbamate, a novel cross-linker for chemical cross-linking/mass spectrometry (XL-MS), to address the instability of DSSO in anhydrous solutions. DSSO-carbamate features improved stability, enhancing cross-link recovery and structural accuracy. When integrated with AlphaFold2, it delivered superior predictions of flexible protein structures. This advancement demonstrates the utility of DSSO-carbamate as a robust tool for XL-MS and protein structure prediction, significantly contributing to structural biology research.
Article in Analytical Chemistry
We developed a new ion-mobility-enabled method for performing native top-down mass spectrometry (MS) with conformation-specific resolution. This approach reveals conformation-linked differences in backbone dissociation, as demonstrated with calmodulin, providing both proteoform variations and structural insights. Additionally, we show its applicability to protein–ligand complexes, enabling component identification and probing ligand-induced structural changes. Our method significantly enhances the structural and functional insights from native top-down MS.
Article in JASMS
We reviewed the literature on the application of Ion-Mobility Mass Spectrometry (IM-MS) to investigate the early oligomerisation of human islet amyloid polypeptide (hIAPP), a key pathological factor in β-cell death in Type II diabetes (T2DM). Our review highlights how IM-MS has enabled characterisation of dynamic oligomer structures, explored the inhibitory effects of metal ions and hIAPP variants, and identified inhibitor modes through spectral fingerprints. We also discuss recent advances in tandem IM-MS and its integration with gas-phase spectroscopy, which promise deeper structural insights into hIAPP oligomers and potential therapeutic strategies for T2DM.
Article in Biophysical Chemistry
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods.