The Mycobacterium tuberculosis very-long-chain fatty acyl-CoA synthetase: structural basis for housing lipid substrates longer than the enzyme

1. Download : Download high-res image (131KB)
2. Download : Download full-size image

Highlights? M. tuberculosis FadD13 is a peripheral membrane protein ? Mutagenesis reveals an arginine-rich patch as the site for membrane interaction ? A hydrophobic tunnel extends from the active site to the positively charged patch ? The architecture lets substrates reside partly in the membrane during catalysis     

PRDM14 Ensures Naive Pluripotency through Dual Regulation of Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells

1. Download : Download high-res image (208KB)
2. Download : Download full-size image

Highlights? Prdm14 expression is important for maintenance of naive pluripotency ? PRDM14 antagonizes FGFR signaling and activates Akt-mTORC1 signaling ? PRDM14 represses de novo DNA methyltransferase expression ? This regulatory input is mediated through recruitment of PRC2     

The Helicobacter pylori virulence effector CagA abrogates human β-defensin 3 expression via inactivation of EGFR signaling

1. Download : Download high-res image (308KB)
2. Download : Download full-size image

Highlights? H. pylori is highly susceptible to the bactericidal activity of hBD3 ? hBD3 is initially induced by H. pylori via activation of EGFR/MAPK/JAK signaling ? H. pylori evades killing by downregulating hBD3 via CagA-mediated SHP-2 activation ? CagA virulence factor is a potent inhibitor of an immune effector mechanism     

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

1. Download : Download high-res image (260KB)
2. Download : Download full-size image

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     

Structure of the MST4 in Complex with MO25 Provides Insights into Its Activation Mechanism

1. Download : Download high-res image (437KB)
2. Download : Download full-size image

Highlights? MO25 forms a stable complex with MST4 to enhance its kinase activity ? Association of MO25 activates MST4 by rotating its αC helix to active conformation ? Kinase-domain-mediated dimerization is required for MST4 trans-autophosphorylation ? MO25-stimulated activation of MST4 promotes apoptosis in HEK293T cells     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

1. Download : Download high-res image (229KB)
2. Download : Download full-size image

Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

RPA Accumulation during Class Switch Recombination Represents 5′–3′ DNA-End Resection during the S–G2/M Phase of the Cell Cycle

1. Download : Download full-size image

Highlights? RPA and Rad51 bind asymmetrically to recombining immunoglobulin genes ? Ig gene DNA breaks are resected as B cells enter the S–G2/M cell-cycle stages ? ATM regulates localized DNA-end resection in G1 ? DNA-end resection in S–G2/M is extensive and ATM independent     

Macrophage autophagy plays a protective role in advanced atherosclerosis

1. Download : Download high-res image (147KB)
2. Download : Download full-size image

Highlights? Proapoptotic oxidative stress induces autophagy in macrophages (M?s) ? Inhibition of autophagy enhances oxidative stress and apoptosis in M?s ? Atheromata of M?-Atg5^?/?Ldlr^?/? mice have increased apoptosis and plaque necrosis ? Apoptotic Atg5^?/? M?s are poorly recognized by phagocytes in vitro and in atheromata     

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

1. Download : Download high-res image (195KB)
2. Download : Download full-size image

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     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

1. Download : Download high-res image (141KB)
2. Download : Download full-size image

Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

Neuronal ER Stress Impedes Myeloid-Cell-Induced Vascular Regeneration through IRE1α Degradation of Netrin-1

1. Download : Download high-res image (338KB)
2. Download : Download full-size image

Highlights? Canonical ER stress pathways are activated in central neurons during hypoxia/ischemia ? The ER stress endoribonuclease IRE1α degrades the neurovascular guidance cue netrin-1 ? Neuronal-derived netrin-1 activates a reparative proangiogenic program in microglial cells ? Neuronal ER stress prevents reparative angiogenesis in the ischemic neural retina     

The Microtubule-Binding Protein Ensconsin Is an Essential Cofactor of Kinesin-1

1. Download : Download high-res image (155KB)
2. Download : Download full-size image

Highlights? Ensconsin is required for cargo transport driven by kinesin-1 ? The C terminus of ensconsin activates kinesin-1; its N terminus binds microtubules ? Kinesin-1 mutants without autoinhibitory activity do not require ensconsin     

Structure of AAV-DJ, a Retargeted Gene Therapy Vector: Cryo-Electron Microscopy at 4.5 Å Resolution

1. Download : Download high-res image (512KB)
2. Download : Download full-size image

Highlights? The 4.5 Å cryo-EM structure of AAV-DJ fully resolves the polypeptide backbone ? Liver tropism selected for in AAV-DJ has not changed the heparin binding site ? Changed conformation in an antigenic loop blocks binding of a neutralizing mAb ? Changed in vivo tropism may result from changed immune interactions     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

1. Download : Download high-res image (202KB)
2. Download : Download full-size image

Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Role of the Mad2 Dimerization Interface in the Spindle Assembly Checkpoint Independent of Kinetochores

1. Download : Download high-res image (371KB)
2. Download : Download full-size image

Highlights? Mad2 overexpression activates the SAC independently from Mad1 in budding yeast ? Mad2 dimerization surface is required for the SAC independently from Mad1 ? Mad2 dimerization downstream of kinetochores is negligible for the SAC ? Mad2 dimerization surface interacts with Mad3 and is required for MCC stability     

EpCAM Is an Endoderm-Specific Wnt Derepressor that Licenses Hepatic Development

1. Download : Download high-res image (176KB)
2. Download : Download full-size image

Highlights? Endodermal EpCAM cell autonomously modulates the Wnt2bb-induced hepatic development ? EpCAM directly binds to Kremen1 and disrupts the Kremen1-Dkk2 interaction ? EpCAM derepresses Lrp6 and allows Lrp6 clustering into active signalosomes ? EpCAM licenses and cooperatively activates Wnt2bb signaling in the endoderm