ScCobB2-mediated Lysine Desuccinylation Regulates Protein Biosynthesis and Carbon Metabolism in Streptomyces coelicolor,

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Highlights

• •Identification of the first evolutionary divergent sirtuin ScCobB2 in bacteria.
• •Implementing a global quantitative succinylome between ΔScCobB2 and WT cells.
• •ScCobB2 regulates S. coelicolor protein biosynthesis and carbon metabolism pathways.
• •The divergent sirtuin enzymes are prevalent in other groups of Actinobacteria.

     

Global Lysine Crotonylation and 2-Hydroxyisobutyrylation in Phenotypically Different Toxoplasma gondii Parasites

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Highlights

• •Quantitative proteomes and epigenetic regulation of T. gondii.
• •Protein crotonylation and 2-hydroxyisobutylation in phenotypically different T. gondii parasites.
• •Regulation of invasion regulation of T. gondii by protein modification.
• •Lysine crotonylation and 2-hydroxyisobutylation regulated in multiple biological processes in phenotypically different T. gondii parasites.

     

Crystal Structure of the O2-Tolerant Membrane-Bound Hydrogenase 1 from Escherichia coli in Complex with Its Cognate Cytochrome b

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Highlights? The structure of a membrane-bound [NiFe]-hydrogenase/cytochrome b complex ? One active hydrogenase is able to “jumpstart” its O₂-inactivated counterpart ? E. coli hydrogenase 1 has a central protective role against O₂-induced cell damage ? The structure defines the hydrogenase/cytochrome b active-interacting surface     

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.

     

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

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Highlights? Splice-isoform switching favors prosurvival BCL2 family expression in human BC ? BC LSCs are quiescent and TKI-resistant in the marrow niche ? Sabutoclax, a pan-BCL2 inhibitor, enhances TKI sensitivity of bone marrow BC LSCs     

Investigating Lactococcus lactis MG1363 Response to Phage p2 Infection at the Proteome Level

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Highlights

• •The proteomes of L. lactis MG1363 and phage p2 at different stages of infection were characterized.
• •16% (226/1412) of the bacterial proteins detected were unique to infected cultures.
• •A targeted approach using synthetic peptides improved the coverage of phage p2 proteome.
• •By means of proteogenomics, we uncovered a conserved phage protein coded by a previously unannotated gene.
• •Deletion of the bacterial gene llmg_0219 (unknown function) impedes phage p2 infection.

     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

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Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development

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Highlights? Wnt2 is required for atrial and inflow tract morphogenesis ? Wnt2 regulates expansion of secondary heart field progenitors ? Defects in Wnt2^?/? mutants can be rescued using Wnt signaling agonists ? Wnt2 cooperates with Gata6 to regulate cardiac inflow tract development     

ASH2L Regulates Ubiquitylation Signaling to MLL: trans-Regulation of H3 K4 Methylation in Higher Eukaryotes

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Highlights? ASH2L WH motif is important for trans-regulation of H3 K4 methylation by H2Bub ? Ub stimulates MLL activity in trans, in contrast to DOT1L regulation by H2Bub ? H2Bub enhances MLL, but not MLL3, methyltransferase activity ? H2Aub directly represses MLL methyltransferase activity     

Genetic Correction of a LRRK2 Mutation in Human iPSCs Links Parkinsonian Neurodegeneration to ERK-Dependent Changes in Gene Expression

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Highlights? hiPSC-derived neurons with LRRK2 G2019S exhibit Parkinsonian neurodegeneration ? Genetic correction of the LRRK2 mutation rescued neurodegenerative phenotypes ? Comparative analysis links LRRK2 G2019S, gene dysregulation, and ERK activation ? ERK-dependent gene dysregulation by LRRK2 G2019S contributes to neurodegeneration     

Conodipine-P1-3, the First Phospholipases A2 Characterized from Injected Cone Snail Venom*

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Highlights

• •Three novel Conodipines P1-3 in the injected venom of Conus purpurascens.
• •Conodipines P1-3 have consensus catalytic characteristics of sPLA₂.
• •We determined multiple modification sites in Conodipines P1-3.
• •Evaluated the activity of Conohyal-P1 by a MS-based method.

     

Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC

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Highlights? Gene expression noise is an efficient means to probe dose responses ? Variability in MYC reveals biphasic E2f1 dose response ? Modeling predicts serum attenuates E2F repression by MYC ? Biphasic expression underlies discrimination of aberrant levels of growth signaling     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

PP2A phosphatase acts upon SAS-5 to ensure centriole formation in C. elegans embryos

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Highlights? PP2A phosphatase is essential for centriole formation in C. elegans ? PP2A subunits genetically and physically interact with the SAS-5/SAS-6 complex ? PP2A-mediated dephosphorylation of SAS-5 is required for SAS-5/SAS-6 centriolar targeting ? Human PP2A is required for HsSAS-6 centriolar targeting and centriole formation     

Identification of Distinct Ligands for the C-type Lectin Receptors Mincle and Dectin-2 in the Pathogenic Fungus Malassezia

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Highlights? Mincle and Dectin-2 cooperatively recognize Malassezia through distinct ligands ? The Mincle ligands in Malassezia are glucosyl- and mannosylglycolipids ? The Dectin-2 ligand in Malassezia is an O-linked mannobiose-rich glycoprotein ? Cytokine response to the respective ligands was impaired in Mincle^?/? and Dectin-2^?/? DCs     

Structure and Ca2+-Binding Properties of the Tandem C2 Domains of E-Syt2

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Carcinogenic Helicobacter pylori Strains Selectively Dysregulate the In Vivo Gastric Proteome,Which May Be Associated with Stomach Cancer Progression,

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Highlights

• •H. pylori dysregulates the in vivo gastric proteome of gerbils in a strain-specific manner.
• •H. pylori increases RABEP2 and G3BP2 levels in cell culture.
• •H. pylori upregulates RABEP2 and G3BP2 in gerbil and human gastric epithelium.
• •Levels of RABEP2 and G3BP2 increase with severity of malignant lesions in vivo.

     

Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of L,D-Transpeptidase 2

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Highlights? The structure of Mtb Ldt_Mt2 shows the binding of a peptidoglycan fragment ? The structure of the complex maps the interaction between acyl donor and enzyme ? Ldts show a conserved C-terminal ykuD domain with a divergent N-terminal domain ? Based on the structure of this complex, a reaction mechanism is proposed