Structural surfaceomics of myeloma models to identify tumor-specific protein conformations

Proteins at the cell surface are promising targets for cancer immunotherapies. While standard surface proteomics can be powerful for target discovery, even more fruitful is identifying cancer-specific surface protein features. To this end, we recently described a technology to identify cancer-specific protein three-dimensional conformations. In “structural surfaceomics”, we integrated XL-MS and surface protein biotinylation to identify the active conformation of integrin beta-2 as a promising cellular therapy target in acute myeloid leukemia (Mandal et al, Nature Cancer (2023)). However, we only applied structural surfaceomics to a single cancer model, and crosslink modeling was done manually. Here, we apply our technology to additional cancer models and implement an automated pipeline for crosslink characterization, AlphaCross-XL (Biswas et al, ASMS abstract (2023)).