Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer,

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Highlights

• •OMICS distinguish cancer cells from resistant or cancer stem cells.
• •Bactericidal antibiotics and mitochondria.
• •Linezolid and anticancer therapy.

     

Surface Loops in a Single SH2 Domain Are Capable of Encoding the Spectrum of Specificity of the SH2 Family,

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Highlights

• •Surface loops play an essential role in SH2 domain specificity.
• •Diverse specificities may be obtained from a single SH2 domain by combinatorial mutations in the EF and BG loops.
• •The specificity of a loop mutant correlates with the sequence characteristics of the bait peptide used in its isolation.

     

Effects of Acetylation and Phosphorylation on Subunit Interactions in Three Large Eukaryotic Complexes

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Highlights

• •Novel PTMs detected in native yeast exosome, RNA polymerase II and proteasome.
• •MD based approach outperforms published tools in predicting PTMs stability effect.
• •Dynamical approach reveals long range effects of PTMs on subunits binding.
• •Acetylations may have a role in local stabilization of protein complex formation.

     

Quantitative Early Auxin Root Proteomics Identifies GAUT10, a Galacturonosyltransferase,as a Novel Regulator of Root Meristem Maintenance

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Highlights

• •Auxin responsive proteins in Arabidopsis roots were identified from 3,514 detected proteins.
• •All six auxin receptors are stable in response to hormone via novel MRM assays.
• •The >100 differentially expressed proteins exhibit dynamic and transient responses to auxin.
• •Phenotypic screening of the top responsive proteins uncovered several novel root mutants.

     

Metabolic,Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*

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Highlights

• •In-depth proteome profiling of primary human myeloma cells
• •Characteristics of myeloma cells are related to hypoxic bone marrow conditions
• •Myeloma cells show specific immune evasion strategies
• •Metabolic adaptations involve tumor and stroma cells

     

DECA,A Comprehensive,Automatic Post-processing Program for HDX-MS Data*

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Highlights

• •Open source software for comprehensive HDX-MS data analysis.
• •Automatic back-exchange correction options.
• •Rigorous statistical analysis of the significance of uptake differences.
• •High quality visualization tools.

     

Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection*

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Highlights

• •Interplay of epithelial cells and internalized S. aureus was dissected over 96 h.
• •Surviving host cells contain nonreplicating bacteria that persists in the cytoplasm.
• •Competition over resources triggers temporal metabolic changes.
• •Metabolic adaptation of host and bacteria determines the outcome of infection.

     

Endoglycosidase S Enables a Highly Simplified Clinical Chemistry Procedure for Direct Assessment of Serum IgG Undergalactosylation in Chronic Inflammatory Disease

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Highlights

• •Selective release of IgG Fc glycans in crude serum by endoglycosidase S.
• •CE-LIF-based measurements of IgG undergalactosylation levels (UGS).
• •UGS as a biomarker: Stratification of non-alcoholic steatohepatitis patients and controls.

     

Glycoproteogenomics: A Frequent Gene Polymorphism Affects the Glycosylation Pattern of the Human Serum Fetuin/α-2-HS-Glycoprotein

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Highlights

• •Frequent genetic polymorphism affects the glycosylation pattern of fetuin.
• •Personalized in-depth proteoform profiling of fetuin purified from 20 donors.
• •Classification of serum donors into three different genotypes.
• •Septic patients show increased level of fucosylation at N-glycolation site N176.

     

Glycan Markers of Human Stem Cells Assigned with Beam Search Arrays,

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Highlights

• •R-10G is a mono-sulfated glycan antigen of human iPS and ES cells on podocalyxin.
• •R-10G and nonsulfated i are reciprocal antigens on type 2 glycan backbones.
• •TRA-1–60 and -81 and FC10.2 are antigens expressed on unsulfated type 1 backbones.
• •These assignments open the way to probing their roles in podocalyxin-signaling.

     

Accurate Estimation of Context-Dependent False Discovery Rates in Top-Down Proteomics

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Highlights

• •To correctly estimate FDR, search context should be considered.
• •FDR is computed at the molecular level reported; e.g., proteoform or protein.
• •Failure to correctly estimate FDR results in >20-fold errors for the data we studied.
• •TDCD_FDR_Calculator is a free tool providing accurate, conservative FDR estimation.

     

Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

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Highlights

• •Quantitative (phoshpo)proteome of primary cell cultures of patient-matched prostate CAF and NPF.
• •Key CAF-associated proteins validated using orthogonal methodologies.
• •LOXL2 inhibitors D-penicillamine and PXS-S2A impaired CAF migration and ECM alignment.
• •Pre-treatment with LOXL2 inhibitors impaired migratory capacity of RWPE-2 cells in co-culture.

     

Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling

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Highlights

• •quantitative phosphoproteome analysis of TDM-activated macrophages.
• •distinct Mincle-dependent and independent phosphorylation and gene regulations.
• •Mincle-dependent activation of PI3K/AKT signaling by TDM.
• •Mincle-independent macrophage response is linked to cell cycle regulation.

     

Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398

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Highlights

• •Proteogenomics and secretome comparison of human and zoonotic Staphylococcus aureus lineages.
• •869 secreted proteins identified in eight S. aureus isolates of CC8, CC22 and CC398.
• •CC398 lower secretion of surface proteins and higher secretion of hemolysins and exoenzymes.
• •Regulatory differences in the secretomes could be linked to lower SigB activity in CC398.

     

MaxQuant.Live Enables Global Targeting of More Than 25,000 Peptides

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Highlights

• •MaxQuant.Live controls Orbitrap mass analyzers in real-time.
• •Freely available apps enable advanced data acquisition strategies.
• •On-the-fly mass, retention time and intensity recalibration.
• •Global targeting unifies shotgun and targeted proteomics.

     

Chromobodies to Quantify Changes of Endogenous Protein Concentration in Living Cells

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Highlights

• •Chromobodies are stabilized by antigen binding in live cells.
• •Monitoring changes of endogenous protein levels in living cells with chromobodies.
• •Broadly applicable system to generate turnover-accelerated chromobodies.
• •Quantification of time- and dose-dependent compound effects.

     

Probing H2O2-mediated Structural Dynamics of the Human 26S Proteasome Using Quantitative Cross-linking Mass Spectrometry (QXL-MS)

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Highlights

• •Two-step cross-linking coupled with affinity purification to facilitate structural analysis of protein complexes.
• •Integrated QXL-MS workflow for studying condition-dependent structural changes of protein complexes.
• •Mechanistic insights on in vivo H₂O₂-induced conformational dynamics of proteasome complexes.

     

Identification of Salivary Biomarkers for Oral Cancer Detection with Untargeted and Targeted Quantitative Proteomics Approaches

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Highlights

• •iTRAQ-based analysis of saliva samples from oral cancer patients.
• •Proteome profiling of saliva samples from patients with oral premalignant lesions.
• •Verification of salivary biomarker candidates with MRM-MS and immunoassays.
• •Identification of salivary proteins as potential biomarkers of oral cancer.