The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme

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Highlights? The first structure of a nuclear PP1 holoenzyme, NIPP1:PP1 ? The NIPP1 helix defines a unique interaction site on PP1 ? Identification of a common PP1-binding pocket, the ΦΦ motif-binding pocket ? Explains the mechanism of nuclear substrate selection by PP1     

Selective and specific inhibition of the plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin

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Highlights? The fungal secondary metabolite Cladosporin inhibits liver- and blood-stage malaria parasites ? Cladosporin specifically targets lysyl-tRNA synthetase (Krs1) ? Cladosporin is >100-fold more potent against parasite Krs1 relative to the human enzyme ? Two amino acids in the Krs1 ATP-binding pocket confer species-selective inhibition     

Functional implications from the Cid1 poly(U) polymerase crystal structure

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Highlights? Our structure identifies the UTP-binding pocket of the Cid1 protein ? The atomic model suggests a central role for the helix 4 ? We suggest that the NRM loop is blocked after triphosphate recognition ? We identify several loops likely involved in the RNA primer association/stabilization     

Cap-assisted internal initiation of translation of histone H4

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Highlights? Two structural elements of histone H4 mRNA drive translation initiation ? Ribosome is tethered by an eIF4E-binding site located in the coding region ? A RNA three-way helix junction element positions ribosome on the start codon ? The m⁷G cap-binding pocket formed by the mRNA controls histone translation     

The Structure of the Tiam1 PDZ Domain/ Phospho-Syndecan1 Complex Reveals a Ligand Conformation that Modulates Protein Dynamics

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Highlights? The Tiam1 PDZ domain preferentially binds a subset of syndecan (SDC) proteins ? The PDZ domain/phospho-SDC1 structure reveals a phosphoryl binding pocket ? Ligand specificity and phosphorylation regulate PDZ/SDC interactions and signaling ? Tiam1 PDZ domain dynamics are ligand-dependent and regulated by phosphorylation     

Molecular mechanism for inhibition of g protein-coupled receptor kinase 2 by a selective RNA aptamer

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Highlights? C13 RNA aptamer variants stabilize GRK2 in a unique and remodeled conformation ? The aptamer positions an adenine nucleotide into the ATP-binding pocket of GRK2 ? Basic residues on an exterior surface of GRK2 facilitate aptamer binding ? The terminal stem of the aptamer indirectly contributes to affinity     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

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Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex     

Structure of a bacteriophytochrome and light-stimulated protomer swapping with a gene repressor

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Highlights? Bacteriophytochrome structure containing photosensory and output transducing domain ? RpBphP1 binds to the cognate repressor RpPpsR2 on illumination with far-red light ? HOS domain is distantly related to Dhp and is essential for binding to the repressor ? Light-induced protomer swapping mechanism between dimers     

A novel aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity

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Highlights? GATA23 is involved in lateral root founder cell specification ? A coordinated migration of pericycle nuclei precedes the first asymmetric division ? An Aux/IAA28-dependent auxin signaling cascade controls GATA23 expression     

Variable lymphocyte receptor recognition of the immunodominant glycoprotein of Bacillus anthracis spores

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Highlights? VLRBs use their C-terminal LRRs and the LRRCT-loop to interact with antigen ? Sequence-related VLRBs exhibit differential recognition of their BclA epitopes ? VLR4 binds a conserved protein epitope, yet is specific for B. anthracis spores     

The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type

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Highlights? MYC and MET affect glucose and glutamine metabolism differently in the liver ? Tissue context affects the outcome of metabolic reprogramming by MYC ? MYC overexpression sensitizes cells to inhibition of Gls1 glutaminase     

Interplay between the Dividing Cell and Its Neighbors Regulates Adherens Junction Formation during Cytokinesis in Epithelial Tissue

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Highlights? During cytokinesis, neighboring cells accumulate MyoII at the edges of the furrow ? MyoII nonautonomously sets the initial geometry of the daughter cell interface ? Neighboring membranes impede adherens junction (AJ) formation until a midbody forms ? Arp2/3-dependent actin accumulation in the dividing cell maintains AJ geometry     

Architecture of a dodecameric bacterial replicative helicase

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Highlights? Crystal structure of the ATPase domain of DnaB from Helicobacter pylori ? MALLS analysis shows that HpDnaB forms dodecamers ? EM reconstruction shows that HpDnaB forms head-to-head double hexamers     

Klf15 orchestrates circadian nitrogen homeostasis

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Highlights? Nitrogen homeostasis exhibits circadian rhythmicity in mammals ? Klf 15 regulates rhythmic amino acid utilization and ammonia detoxification ? Krüppel-like factor 15 is regulated by the circadian clock ? Feeding is a major external cue regulating Klf15 rhythmicity and nitrogen homeostasis     

Trachea-Derived Dpp Controls Adult Midgut Homeostasis in Drosophila

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Highlights? Trachea-derived Dpp/Bmp is required for midgut homeostasis ? Dpp expressed in tracheal cells reach intestinal cells through visceral muscles ? Dpp signaling is activated in enterocytes (ECs) in the Drosophila adult midgut ? Dpp signaling stabilizes ECs to restrict intestinal stem cell proliferation     

Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration

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Highlights? Pax7⁺ skeletal satellite cells regenerate muscle in their endogenous environment ? Quiescent satellite cells express the RTK inhibitor Spry1 ? Spry1 is needed for satellite cells to return to quiescence after muscle injury ? Deletion of Spry1 in satellite cells depletes the muscle stem cell pool     

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational Derepression of HIF2α

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Highlights? Irp1 deficiency causes polycythemia and pulmonary hypertension ? Irp1 regulates HIF2α translation and expression of EPO and endothelin 1 ? Irp1 represses erythropoiesis to protect tissue iron levels during iron deficiency ? A low-iron diet worsens polycythemia and causes sudden death in Irp1?/? animals     

The bacterial stressosome: a modular system that has been adapted to control secondary messenger signaling

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Highlights? Regulation of cyclic di-GMP biosynthesis in Moorella thermoacetica ? Stressosome signal transduction and resetting ? X-ray crystal structure of type 2C phosphatase MtX ? X-ray crystal structures of phosphorylated MtS and the N-terminal domain of MtR     

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