Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling

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Highlights

• •Quantitative proteomes of the cellular surface changes induced by mTORC1 signaling.
• •Hit validation in human cancer cell lines and biopsies.
• •Functional studies showing new drug targets to which cancer cells with hyperactive mTORC1 may be addicted.
• •A new paradigm for drug development, namely targeting cell surface proteins regulated by mTORC1.

     

Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State

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Highlights

• •CD73 is one of the most upregulated proteins in the radioresistant cells.
• •CD73 upregulation confers radioresistance and irradiation-induced apoptosis.
• •CD73 confers radioresistance potentially through inactivating protein BAD.
• •Elevated CD73 is required for maintaining the resistant cells in a mesenchymal state.

     

Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons

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Highlights

• •Integrated phosphoproteomics and analyses of newly synthesized proteins in neurons.
• •Resource of temporal mGluR-induced signaling pathways upon DHPG stimulation.
• •Validation of PKC, MAPK1, CAMKIIa, and CDK2 in mGluR-activation and signaling.
• •Validation of Intersectin-1 in DHPG-induced AMPAR internalization.

     

The Mouse Heart Mitochondria N Terminome Provides Insights into ClpXP-Mediated Proteolysis

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Highlights

• •Mitochondrial heart N terminome shows aminopeptidase processing after MTS cleavage.
• •CLPP-deficiency alters protein processing patterns in mouse heart mitochondria.
• •Candidate substrates identified by N termini accumulation and interaction with inactive ClpXP.
• •UQCRC1, HSPA9 and OAT validated biochemically as high confidence ClpXP substrates.

     

Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking Antibodies

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Highlights

• •Characterization of 12 proteins from across the P. falciparum sexual-stages as possible TBV targets.
• •Heterologously expressed recombinant proteins recapitulate native parasite epitopes.
• •Some recombinant proteins exhibit immunoreactivity when tested against sera from individuals from malaria-endemic Burkina Faso and Mali.
• •Purified IgG against the antigen enolase moderately inhibits parasite development in the mosquito midgut.

     

MaXLinker: Proteome-wide Cross-link Identifications with High Specificity and Sensitivity

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Highlights

• •New quality assessment metrics to evaluate proteome-wide cross-linking mass spectrometry (XL-MS) data sets.
• •New “MS3-centric” cross-link search engine named MaXLinker with high sensitivity and specificity.
• •More than 9300 cross-links from our human proteome-wide XL-MS study.
• •Orthogonal experimental validation of novel interactions identified in our study.

     

Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity

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Highlights

• •Quantitative proteome interactions with 5 different C9ORF72 dipolypeptides (DPRs).
• •The arg-rich DPRs promiscuously bound to the proteome compared with the other DPRs.
• •Long repeat lengths of arg-rich DPRs, but not short lengths, stalled ribosomes.
• •The arg-rich DPRs also reduced arginine methylation and actin cytoskeleton assembly.

     

Perlecan Knockdown Significantly Alters Extracellular Matrix Composition and Organization During Cartilage Development

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Highlights

• •Matrisome content significantly changes with development and perlecan knockdown.
• •Chondrocytes respond to perlecan deficiency by increasing bulk matrisome secretion.
• •Decreased stiffness may be explained by atypical glycosaminoglycan deposition.
• •Elevated COL10A1 expression and chondrocyte hypertrophy indicate early ossification.

     

Molecular Dynamics Simulation-assisted Ionic Liquid Screening for Deep Coverage Proteome Analysis

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Highlights

• •Mechanistic insights into ionic liquids and proteins at molecular level.
• •Extractants prescreen for proteome analysis with MD simulation system.
• •A loss-less sample preparation method developed for in-depth proteome profiling.
• •Over 3,300 proteins were confidently identified from 1,000 HeLa cells in a 1 h run.
• •Label-free quantitative proteome analysis of human liver cancer tissues.

     

High-speed Analysis of Large Sample Sets – How Can This Key Aspect of the Omics Be Achieved?

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Highlights

• •Future proteomic analyses for longitudinal studies and P4 medicine arguably require ≥1M samples/day.
• •Proteome depth/coverage is commonly the focus whereas analytical speed is typically neglected.
• •A compromise between analytical depth and speed is needed for future large-scale studies.
• •Ultrahigh-speed ‘omic’ analyses require tools that are intrinsically fast such as laser-based MS.

     

Organellar Maps Through Proteomic Profiling – A Conceptual Guide

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Highlights

• •Organelle profiling maps capture localizations of 1000s of proteins in one experiment.
• •Comparing maps +/− perturbation reveals disease mechanisms & cellular responses.
• •A conceptual guide to planning and interpreting organellar profiling experiments.
• •A cross-study consensus set of human organellar marker proteins.

     

Sample Preparation by Easy Extraction and Digestion (SPEED) - A Universal,Rapid, and Detergent-free Protocol for Proteomics Based on Acid Extraction

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Highlights

• •Universal and detergent-free proteomic sample preparation.
• •Based on three simple mandatory steps (acidification, neutralization, digestion).
• •Enhances proteome coverage especially for challenging samples.
• •Improves quantitative reproducibility compared with ISD-Urea, FASP and SP3.

     

OpenPepXL: An Open-Source Tool for Sensitive Identification of Cross-Linked Peptides in XL-MS

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Highlights

• •OpenPepXL is a new XL-MS identification tool with a high sensitivity.
• •It is available for all common operating systems and remote computing environments.
• •OpenPepXL is open source and supports open OpenPepXL is available as part of OpenMS data formats like mzML and mzIdentML.
• •at https://www.openms.de/openpepxl.

     

Data,Reagents, Assays and Merits of Proteomics for SARS-CoV-2 Research and Testing

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Highlights

• •In-depth proteomes of 4 SARS-CoV-2 cell line models (Vero E6, Calu-3, Caco-2, A549).
• •Proteomic evidence for thousands of Chlorocebus sabaeus proteins.
• •Proteomic response of Vero E6 cells to SARS-CoV-2 infection.
• •Synthetic peptides, spectral libraries, and targeted assays for SARS-CoV-2 proteins.

     

Single-cell Proteomics: Progress and Prospects

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Highlights

• •Label-free and isobaric labeling approaches for in-depth profiling of single cells.
• •Miniaturization and simplification of sample processing reduce surface losses.
• •Nanoflow separations enhance ionization efficiency and reduced chemical noise.
• •Ultrasensitive mass spectrometry and gas-phase separation add selectivity.

     

Mass Spectrometry Based Immunopeptidomics Leads to Robust Predictions of Phosphorylated HLA Class I Ligands

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Highlights

• •Curation of 2066 phosphorylated HLA class I peptides from immunopeptidomics data.
• •Determination of 22 HLA class I binding motifs for phosphorylated peptides.
• •Observation of a higher frequency of phosphorylated ligands binding HLA-C molecules.
• •Development of a predictor of phosphorylated peptide interactions with HLA class I.

     

Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing

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Highlights

• •Quantitative proteome of neonatal, young, and aged OPCs.
• •50% of the proteome is differentially expressed between neonatal and adult OPCs.
• •Myelin proteins are increased, and cholesterol synthesis proteins decreased with age.
• •Proteins associated with other neurodegenerative diseases are increased in aged OPCs.

     

PolySTest: Robust Statistical Testing of Proteomics Data with Missing Values Improves Detection of Biologically Relevant Features

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Highlights

• •Novel statistical test combining missingness and quantitative profiles.
• •Unification of different statistical tests into a PolySTest FDR provides higher robustness and confidence.
• •PolySTest provides higher coverage of relevant biological pathways.
• •User-friendly interactive web service for statistical analysis and visualization.

     

Stoichiometry of Nucleotide Binding to Proteasome AAA+ ATPase Hexamer Established by Native Mass Spectrometry

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Highlights

• •All six binding sites in PAN^WT are occupied by ADP- or ATP-type nucleotides.
• •PAN^KA Walker A mutant substoichiometrically binds ATP- but not ADP-type nucleotides.
• •PAN hexamer dissociation of the solution origin characteristics was observed in MS.
• •We posit that the PAN hexamer dissociation proceeds within the ESI droplets.