In Brief CRTC2 (with CREB1) in glucose metabolism is well studied; however, further studies are required to delineate the metabolic regulatory aspects. Here, using various biochemical and computational tools, it has been identified that CRTC2 along with SREBF1 regulates targeted genes to fine-tune the metabolic response under various conditions. This should further highlight the tight regulation of glucose metabolism and could be therapeutically used for various diseases ..read more

We present an integrated immunopeptidomics and proteomics study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to comprehensively decipher the changes in host cells in response to viral infection. Immunopeptidomics analysis identified viral antigens presented by host cells through both class I and class II MHC system for recognition by the adaptive immune system. The host proteome changes were characterized by quantitative proteomics and glycoproteomics and from these data, the activation of toll-like receptor 3–interferon pathway was identified ..read more

In Brief Compared to the total number of mammalian genes, the structural diversity of glycoproteins as a consequence of posttranslational glycosylation is enormous. We propose an integrated HPLC-mass spectrometry approach to explore the highly glycosylated protein recombinant acid alpha-glucosidase (Myozyme). The glycosylation complexity of this protein is reflected in a huge chemical space of more than 40,000 glycoforms, which were experimentally revealed through HPLC-mass spectrometry analyses and bioinformatic data integration at different structural levels of released glycans, glycopeptide ..read more

In Brief Given the high relapse of TKI resistance caused by EGFR secondary mutation, T790M, EGFR mutant interactomes are constructed in four patient-derived NSCLC cells. The T790M rewired EGFR interactome in diverse subcellular localization and shifted EGFR trafficking routes. The gefitinib treatment activated autophagy pathway in TKI-resistant cells, instead of EGFR recycling Rab7 ubiquitination in TKI-sensitive cells. This first functional link between the mutation-mediated PPI and drug resistance behind the long-standing clinical burden may provide opportunities to develop novel therapeutic ..read more

In Brief A guideline study for choosing DIA software tools for both experienced and novice users. Evaluation of 5 DIA tools (OpenSWATH, EncyclopeDIA, Skyline, DIA-NN, Spectronaut) in 6 different data sets, with 12 libraries for 34 conditions. The library-free approach excels when the spectral library size is limited, yet building a comprehensive library remains advantageous for most DIA analyses ..read more

In Brief We analyzed clinical cholesteatoma specimens and paired ear canal skin with MS-based proteomics and bioinformatics, revealed SNCA was a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under inflammatory stimulation, in part ..read more

In Brief In this work, we describe our computational workflow for statistical analysis of thermal proteome profiling data known as InflectSSP. InflectSSP has been optimized for sensitive and reproducible detection and prioritization of protein melt shift changes in biological thermal proteome profiling datasets. Analysis of induction of the unfolded protein response with the small molecule inhibitor thapsigargin using InflectSSP revealed significant melt shift changes that shed new light on the potential mechanisms of action of inhibition of the ER calcium channel SERCA2 ..read more

In Brief Myeloid-derived suppressor cells (MDSCs) counteract the immune system when fighting cancer. Krumm . screened 21,000 compounds in T-cell coculture system in search for modulators of MDSC. They identified Acyp1 and Cd74 as potential targets of the most interesting compound by chemical proteomics. Characterization of the cellular response by (phospho-)proteomics and functional assays revealed upregulation of cellular reactive oxygen species metabolism as a likely mode of action of this MDSC modulator ..read more

deeply profile the free milk glycomes of nine understudied mammalian species. They uncover >100 novel structures that include unusual motifs, such as the widespread use of LacdiNAc and glucuronic acid. This expands known milk oligosaccharide diversity by >15%. Functional experiments indicate potent immunomodulatory effects of novel glucuronic acid–containing milk oligosaccharides. Through contextualization with literature data, they provide an exhaustive overview of milk glycan biodiversity ..read more

In Brief Using the TMT-LC/LC–MS/MS method and a TMTc-based strategy to correct for ratio compression, we analyzed detergent-insoluble proteome from 30 human AD and control brain samples. We identified 84 proteins enriched in the detergent-insoluble fraction, accumulated in AD, and mostly containing low-complexity regions. Our study highlights AD pathological hallmarks resistant to detergent extraction, providing a list of proteins and pathways exclusively present in the detergent-insoluble proteome ..read more