Nonsynaptic Plasticity Underlies a Compartmentalized Increase in Synaptic Efficacy after Classical Conditioning

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Highlights? Classical conditioning reduces attenuation of axonal calcium transients ? Depolarization also reduces spike attenuation in the same axon ? Blocking of potassium A current has the same effect as training or depolarization ? Training and depolarization only affect a specific branch of the neuron’s axon     

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     

DNA Quality Control by a Lesion Sensor Pocket of the Xeroderma Pigmentosum Group D Helicase Subunit of TFIIH

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Highlights? Amino acid changes near the central pore of XPD confer defective excision repair ? These mutants retain DNA helicase activity when tested in an archaeal framework ? The mutants are unable to sense lesions during their ATP-driven tracking movement ? The mutants are unable to build a stable demarcation complex at DNA lesion sites     

Disease mutations in the ryanodine receptor central region: crystal structures of a phosphorylation hot spot domain

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Highlights? Crystal structures of a central RyR domain contain phosphorylation sites ? Eleven RyR1 disease mutations cluster on two opposite faces of the domain ? The RyR1 L2867G mutation causes a drastic destabilization ? In vitro phosphorylation identifies 5 PKA and 4 CaMKII targets     

Enteric neurons and systemic signals couple nutritional and reproductive status with intestinal homeostasis

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Highlights? A metabolic behavior revealing a key homeostatic role for the invertebrate intestine ? Enteric neurons couple reproductive state with intestinal physiology ? An insulinergic brain-gut neuronal circuit adjusts feeding to nutritional conditions ? A vasopressin-like system of central neurons is essential for water homeostasis     

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

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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 CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b

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Highlights? The CDK9 C-terminal tail is important for the catalytic mechanism ? CDK9 phosphorylates the CTD in a nonprocessive manner ? The CDK9 tail folds over the ATP binding site during the catalytic cycle     

Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase

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Highlights? bAvd forms a highly positively charged pentameric barrel ? bAvd binds both DNA and RNA, but without sequence preference ? The coding sequence for bAvd serves dual purposes ? The interaction of bAvd with bRT is likely to be important for retrohoming     

Plasma Membrane Tethering of the Cortical ER Necessitates Its Finely Reticulated Architecture

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Highlights? The VAP proteins sustain the ER-plasma membrane attachment in fission yeast ? Footprint of the ER on the cortex is functionally insulated from the cytosol ? Division-site placement requires a patchwork of cortical sites accessible to cytosol     

A Network Model of the Molecular Organization of Chromatin in Drosophila

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Highlights? DamID identifies 42 previously unknown chromatin proteins ? Binding maps of new and known chromatin components yield a chromatin network model ? The network model predicts functions of most of the 42 new chromatin proteins ? The chromatin protein network is functionally compartmentalized     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Functional Insights from the Crystal Structure of the N-Terminal Domain of the Prototypical Toll Receptor

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Highlights? The N-terminal cap of Toll adopts a new fold ? It resembles a duplicated beta hairpin structure with three disulphide bonds ? Toll LRRNT cap is not critical for Spätzle binding ? The first 13 LRRs are sufficient for Spätzle binding     

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     

Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine

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Highlights? The structure of ketamine-bound GLIC reveals an anesthetic binding site ? The study provides compelling evidence for allosteric inhibition by anesthetics ? Ketamine inhibition on GLIC is similar to competitive antagonist action on nAChRs ? Ketamine directly acts on pLGICs in addition to NMDA receptors     

Structure and Dynamics of the Second CARD of Human RIG-I Provide Mechanistic Insights into Regulation of RIG-I Activation

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Highlights? The structure of a CARD of human RIG-I ? The mechanism and structural role of phosphorylation are revealed ? In trans interaction with the Helicase and regulatory domains is shown ? Lys172 lies in proximity to the CARD2:helicase-CTD interface     

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

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Highlights? Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ? Solution biophysical analysis of ATP-dependent RIG-I conformational change ? The structural basis for ATP-stimulated RIG-I activation     

Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity

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Highlights? EM structure of the CMR complex for viral RNA degradation has been determined ? The crRNA content of CMR has been analyzed by deep sequencing ? Target RNA cleavage by CMR is sequence dependent     

Allosteric Mechanism Controls Traffic in the Chaperone/Usher Pathway

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Highlights? Allosteric mechanism controls traffic in the chaperone/usher pathway ? Usher-binding site in free chaperone is conformationally locked ? Subunit binding opens the lock in the chaperone, allowing usher targeting     

Zinc Drives a Tertiary Fold in the Prion Protein with Familial Disease Mutation Sites at the Interface

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Highlights? Zinc binds to the prion protein octarepeat domain ? The zinc-bound octarepeat makes a tertiary contact to C-terminal helices 2 and 3 ? The encompassed surface carries a majority of the mutations in familial prion disease ? Familial mutations weaken this zinc-driven tertiary contact     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11