The AAA+ protein unfolding motor ClpX grips substrates with the uppermost part of its substrate-binding pore, and requires interactions with hydrophobic amino acid side chains to operate with optimal efficiency.
The structure of a light-sensitive G protein-coupled receptor in complex with a Gi-protein heterotrimer provides a structural foundation for the role of the receptor C-terminal tail in scaffolding and signaling.
In multi-channel sensory systems, gain adaptation can help maintain not only coding capacity across changes in signal intensity, but also combinatorial representations of odor identity.
RSV's unique ability to co-opt host cell mitochondria to facilitate viral infection reveals the RSV-mitochondrial interface as a viable target for therapeutic intervention.
Mohammed Jamshad, Timothy J Knowles ... Damon Huber
The interaction of SecA with its substrate proteins is regulated by its evolutionarily conserved C-terminal tail, which autoinhibits SecA unless SecA binds to the ribosome.
Facing discrepancies in the sensory environment, multisensory information is combined in the medial superior parietal cortex to guide immediate judgements and to also adjust subsequent unisensory perception.
Vivekanandan Shanmuganathan, Nina Schiller ... Roland Beckmann
Two integrated approaches shed light on how XBP1 arrest peptide induces intermediate level of translational pausing and identify hotspot positions to make it stronger.
The microtubule organizing potential of the centrosome is inactivated in a stepwise process through phosphatase activity and mechanical disruption to remove an aging matrix of proteins.
ESCRT-III heteropolymers utilize non-specific lateral electrostatic interactions to recognize one another, which may enable the polymers to slide along one another and adapt to different curvatures.
Joana R Carvalho, Isabela C Fortunato ... Claudio A Franco
Analysis of axial polarity distributions shows that Wnt5a regulates collective cell migration in vivo by stabilizing vinculin at adherens junctions and fine-tuning mechanocoupling between neighbouring cells.
A series of genetically-encoded fluorescent reporters that allow imaging of neuropeptide release in vivo, with sub-second temporal and nerve terminal-level spatial resolution are developed.
Dasan Mary Cibi, Masum M Mia ... Manvendra K Singh
The identification of the splicing code and all the required components of alternative splicing will be crucial for a comprehensive understanding of this process in the neural crest cell biology.
In a developing yeast colony, cells go from homogeneous states to spatially organized, specialized metabolic states, and the new metabolic states depend on resources produced by the original state.
Pranesh Padmanabhan, Ramón Martínez-Mármol ... Frédéric A Meunier
Super-resolution imaging reveals that the microtubule-associated protein Tau regulates the Fyn kinase organisation in dendrites, and that the frontotemporal dementia mutant Tau promotes aberrant Fyn clustering, potentially leading to synaptic dysfunction.
Sasha A Langley, Karen H Miga ... Charles H Langley
Genomic polymorphism across centromeric regions of humans is organized into large-scale haplotypes with great diversity, including entire Neanderthal centromeres.
Sophie A Montandon, Anamarija Fofonjka, Michel C Milinkovitch
Robust wrinkling pattern of the frilled dragon’s spectacular erectile ruff emerges from an elastic instability during homogeneous growth of the embryonic neck fold frustrated by its attachment to adjacent tissues.
Kelly M Storek, Joyce Chan ... Steven T Rutherford
Dispensable loops shield the functionally-important extracellular loops of the essential Gram-negative bacterial outer membrane protein LptD from antibody interference.
A statistical method for summarizing single-cell gene expression data identifies normal and disease-specific transcriptional programs from an atlas of 57,600 cells.
Manuel Gálvez-Santisteban, Danni Chen ... Neil C Chi
The heart is able to sense and adaptively respond to environmental changes due to cardiac injury through flow-mediated mechanisms that regulate cardiomyocyte reprogramming and regeneration.
Multi-site FRET measurements of moPrP oligomerization at low pH indicate that major conformational changes take place as monomers reversibly transform into large oligomers, which subsequently disassemble reversibly into small oligomers.
Michael P Meers, Terri D Bryson ... Steven Henikoff
Enhancements to the CUT&RUN antibody-targeted nuclease strategy for chromatin profiling include an improved affinity-cleavage fusion protein and digestion protocol, and a simplified calibration strategy.
Anchoring of proteins to the cell membrane through the glycosylphosphatidylinositol (GPI) anchor is critical for the survival of the cells that will give rise to the brain and face.
Avia Mizrachi, Shiri Graff van Creveld ... Assaf Vardi
Single-cell analysis of the chloroplast redox response to high light and oxidative stress revealed light-dependent heterogeneity, and was linked to cell fate determination within isogenic diatom populations.
The identification of ACNQ as an extracellular electron shuttle solves a longstanding problem in bacterial physiology and provides new tool for bioenergy development.
Structural, computational and functional approaches reveal the role of an extended acidic chamber near the nucleotide binding site in activation of P2X3 receptor channels by divalent-bound ATP.
Delay-period activity of anterior piriform cortex is important for working memory tasks requiring active maintenance and encodes the maintained information.
Christina Chatzi, Yingyu Zhang ... Gary L Westbrook
Single episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.
Hatice Duygu Saatcioglu, Motohiro Kano ... David Pépin
Single-cell RNA sequencing of neonatal uterus revealed an Misr2+ endometrial stromal progenitor whose inhibition by ectopic administration of MIS caused uterine hypoplasia and infertility in adulthood.
Samantha Del Borrello, Margot Lautens ... Andrew G Fraser
Parasitic helminths infect over a billion humans and use unusual anaerobic metabolism that needs a rare electron carrier, Rhodoquinone (RQ), whose synthesis requires the kynurenine pathway of tryptophan degradation.
José-Maria Moreira, Pavel M Itskov ... Carlos Ribeiro
The optoPAD system combines real-time behavioral analysis with optogenetic manipulations to study how animals adapt to dynamic gustatory environments and to identify the circuit basis of feeding.
The sharp expression pattern driven by a classic, simple animal enhancer is determined by multiple molecular mechanisms, not only cooperative binding of the activating transcription factor as was previously thought.
Emilio Salinas, Benjamin R Steinberg ... Terrence R Stanford
Looking away from a salient visual stimulus pits the reflexive urge to look toward it against the voluntary intention not to, and this conflict is resolved within tens of milliseconds.
Molecular dissection of Frizzled, Reck, and Wnt7a provides critical insight into the long-standing question of ligand-receptor specificity in the field of Wnt signaling.
Systematic in vivo analysis reveals the divergent engagement of Plexin B structural motifs in distinct neurodevelopmental processes and a regulatory role of convertase cleavage in Plexin B signaling.
Madhusudhan Srinivasan, Naomi J Petela ... Kim A Nasmyth
In G1 cells, Scc2 loads and maintains cohesin on chromosomes by counteracting a Wapl-independent releasing activity, which is neutralized in S phase by CDK1.
Martin H Fabry, Filippo Ciabrelli ... Benjamin Czech
A member of the Drosophila Nuclear Export Factor (Nxf) family, Nxf2, forms part of the piRNA-dependent co-transcriptional silencing complex and is essential for transposon repression in fly ovaries.
We are writing to respond to the comment by Gapsys and de Groot, 2019 on our article about molecular dynamics simulations of human hemoglobin (El Hage et al., 2018).
A hub in the rostral anterior cingulate cortex receives unusually high and functionally diverse inputs, providing a biological interface between motivation, incentive based learning, and decision making.
In Streptomyces, the nucleoid-associated protein Lsr2 functions as a xenogenic silencer of foreign genes, and as a metabolic gatekeeper, repressing expression of both cryptic and well-studied specialized metabolic biosynthetic clusters.
Muscarinic acetylcholine receptor type A in adult Drosophila inhibits Kenyon cells, and is required for aversive olfactory learning and learning-associated synaptic depression between Kenyon cells and their output neurons.
Cuttlefish embryos reveal that cephalopod mollusks evolved specialized arms and tentacles by activating the same genetic circuits that control development of limbs in arthropods and vertebrates.
In natural pathogen populations opportunities for sexual outcrossing vary, leading to spatial variation in genetic diversity and between-season survival.
VRAC activation, observed with a FRET sensor of intracellular LRRC8-domains movement during gating and by fluorometry, requires plasma membrane localization and diacylglycerol signaling, but is independent of intracellular ionic strength.
Jeong Min Chung, Michael J Sheedlo ... Melanie D Ohi
The Helicobacter pylori Cag T4SS has unique structural features, including unexpected symmetry mismatch between sub-complexes, with implications for protein secretion.
Joshua S Talboom, Asta Håberg ... Matthew J Huentelman
An internet-based cohort study of paired associate learning shows that a first-degree family history of dementia is associated with lowered performance, an effect modified by apolipoprotein E genotype and diabetes.
Allison W Roberts, Lauren M Popov ... Jeffery S Cox
Combination of stem cell engineering and CRISPR technologies created a facile method to genetically manipulate macrophages, a multifunctional cell type that plays critical roles in immunity, cancer, and tissue homeostasis.
Hair cell survival and mitochondrial function is supported by an extracellular stimulator of IGF1 signaling, the protease pregnancy-associated plasma protein-aa.
Franziska Mohring, Melissa Natalie Hart ... Robert William Moon
Optimised genome editing in P. knowlesi enables transgenic expression of a lead P. vivax vaccine candidate, revealing roles in host cell tropisms and providing tools for scalable vaccine efficacy testing.
Aqueous solubility of cystic fibrosis drug ivacaftor is ~200-fold lower, whereas the potency of its stimulatory effect on the CFTR channel is >100-fold higher, than reported, and is fully reversible.
Claudia Cattoglio, Iryna Pustova ... Anders S Hansen
Absolute quantification of CTCF and cohesin reveals quantitative constraints on 3D genome organization and illuminates the molecular architecture of the cohesin complex.
Johann Holzmann, Antonio Z Politi ... Jan-Michael Peters
Absolute quantification of cohesin, CTCF, NIPBL, WAPL and sororin in HeLa cells implies that some genomic cohesin and CTCF enrichment sites are unoccupied at any one time.
Mirjam Hunziker, Jonas Barandun ... Sebastian Klinge
Mass spectrometry analysis of purified pre-ribosomal RNAs shows that stable ribosomal RNA domains independently recruit assembly factors, and the cryo-EM structure of the 5' ETS ribonucleoprotein reveals regulatory conformational switches.
Maria Azkanaz, Aida Rodríguez López ... Vincent van den Boom
Heat shock induces relocalization of epigenetic modifiers to the nucleolus, which acts as a dedicated protein quality control center that is indispensable for recovery of epigenetic regulators and epigenetic modifications.
Mohsen Jamali, Jerome Carriot ... Kathleen E Cullen
Through different coding strategies, irregular and regular otolith afferents preferentially encode translational self-motion and changes in static head orientation relative to gravity.
A novel metabolic network analysis method enables large-scale computational predictions of biosynthetic capabilities across the human oral microbiome, revealing a unique cluster of fastidious microorganisms and potential metabolic interdependencies.
Activity in the dorsomedial prefrontal cortex encodes relative subjective value in a common neural code across decision-making for self and other and across tasks with divergent cognitive requirements.
Recruitment of HOPS tethering complex to target membranes to promote vesicle fusions requires proper complex assembly and specific small GTPases, and HOPS is not transformed from the related miniCORVET complex.
Heme-dependent feedback inhibition of rate-limiting ALA-synthesis of plant tetrapyrrole biosynthesis depends on binding of heme to glutamyl-tRNA reductase-binding protein.
Even moderate winds cause auks to abort landing attempts at nest-sites, and as a result, wind characteristics may affect where these, and other seabirds, choose to breed.
Meenakshi Prajapati-DiNubila, Ana Benito-Gonzalez ... Angelika Doetzlhofer
Opposing gradients of activin A and follistatin within the spiral shaped mammalian cochlea instruct the graded pattern of mechano-sensory hair cell formation.
Early in mammalian epidermal development, basal epidermal progenitor cells utilize packing and three-dimensional geometry, rather than cortical polarity cues, to inform division orientation and progenitor cell fate.
Drosophila use distinct sensory mechanisms to detect and integrate the same tactile and taste information in two decision-making tasks that serve two different purposes.
To protect their food and themselves against detrimental mould fungi, the eggs of a wasp species synthesize and emit remarkable amounts of gaseous nitrogen oxides that are highly effective antimicrobials.
A network of the gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs and supports the generation of mechanistic hypotheses of microbiome metabolic phenotypes that shape human biology.
Newly discovered interaction between fission yeast SPB and animal centriole components reveals that pericentrin not only functions as a microtubule-nucleator, but also promotes centriole assembly in animals.
Vamsi K Daliparthi, Ryosuke O Tachibana ... Todd F Roberts
Precisely sequenced patterns of neuronal activity associated with the production of a skilled behavior begin and end as part of orchestrated activity across functionally diverse populations of cortical premotor neurons.
Proinsulin misfolding, an established cause of diabetes in patients with INS gene mutations, is now observed in normal human pancreatic islets, and rodents with genetic predisposition to type 2 diabetes.
Structural and biochemical studies indicate that AAA+ ATPase employ a general mechanism to translocate a variety of substrates, including extended polypeptides, hairpins, crosslinked chains, and chains conjugated to other molecules.
The major protein disulfide isomerase family member, PDIA1, is essential in beta cells of mice fed a high-fat diet to maintain glucose homeostasis, proinsulin maturation and organelle integrity.
Justyna B Startek, Brett Boonen ... Karel Talavera
The activation and membrane localization of the broadly-tuned noxious chemosensory cation channel TRPA1 are regulated by direct interactions with cholesterol via CRAC motifs in transmembane segments 2 and 4.
Elvira Diamantopoulou, Sarah Baxendale ... Tanya T Whitfield
Results of a zebrafish whole-animal chemical screen for compounds that can rescue ear and myelination defects in an adhesion GPCR (Adgrg6/Gpr126) mutant.
Savani Anbalagan, Janna Blechman ... Gil Levkowitz
Real-time monitoring of oxytocin-loaded vesicles and synaptic actin dynamics in zebrafish reveal that Slit3-Robo2-Cdc42 signalling maintains steady-state levels of mature oxytocin neuropeptide readily primed to be secreted upon physiological demand.
Jenna R Christensen, Kaitlin E Homa ... David R Kovar
The contractile ring actin binding proteins tropomyosin Cdc8 and a-actinin Ain1 synergize to effectively compete with the endocytic actin patch protein fimbrin Fim1 for associating with F-actin networks.
The phase of a neuron in an oscillatory network can remain independent of network frequency when synaptic input strength and peak phase are adjusted in a frequency-dependent manner.
Ernesto Manzo, Ileana Lorenzini ... Daniela C Zarnescu
Degenerating motor neurons compensate for energetic deficits by upregulating glycolysis in flies and humans, with increased glucose availability improving locomotor function and lifespan in flies.
Fabian Wehnekamp, Gabriela Plucińska ... Don C Lamb
The ability to follow single objects in 3D in a living organism with high spatiotemporal resolution opens new possibilities for quantitative biophysical studies of complex systems in their physiological context.
Eduardo A Bignon, Amelina Albornoz ... Nicole D Tischler
Hantavirus spikes are related laterally by 2-fold Gc contacts that can be disulfide-linked and display a temperature-dependent dynamic behavior at neutral pH, exposing and masking the Gc fusion loops.
Timothy S Strutzenberg, Ruben D Garcia-Ordonez ... Patrick R Griffin
Unique methodology was used to generate a large HDX-MS dataset to inform ligand-mediated activation of RORγ, an approach that can be extended to other nuclear receptors with unresolved ligand-dependent activities.
Justin J Grassmeyer, Asia L Cahill ... Wallace B Thoreson
The vesicular Ca2+ sensor synaptotagmin-1 regulates both fast phasic and slow tonic glutamate release at ribbon synapses of rod and cone photoreceptor cells.
Verena Dederer, Anton Khmelinskii ... Marius K Lemberg
The endoplasmic reticulum E3 ubiquitin ligase Doa10 and the mitochondrial AAA-ATPase Msp1 govern targeting fidelity of outer mitochondrial tail-anchored proteins by controlling cytoplasmic concentration and extracting mistargeted and orphan species.
Vanessa A Gutzeit, Jordana Thibado ... Joshua Levitz
Single molecule subunit counting, FRET and electrophysiology experiments reveal that metabotropic glutamate receptor subunits interact and rearrange at the level of the transmembrane domains in response to allosteric modulators.
David O Ajasin, Vasudev R Rao ... Vinayaka R Prasad
Effect of CCL2 on HIV-1 replication is mediated by mobilization of ALIX from F-actin leading to enhanced virion release and improved fitness and this requires the Gag late motif, LYPX.
Par-complex-dependent cell polarity can be cell-autonomously conferred to non-polar Drosophila S2 cells, unveiling temporal patterns toward the cortical localization of Par-complex aggregates that include a meshwork containing unit segments.
The modularity and unequivocal input/response of Notch signaling are harnessed to measure cell-surface shedding of diverse transmembrane receptors to identify new proteolytic switches and detect modulation of proteolysis by therapeutics.
Previously uncharacterized long repeat sequences are associated with significant genome variation that can increase fitness and promote antifungal drug resistance in diverse isolates of Candida albicans.
A behavioral model, neuronal recordings, and electrical microstimulation reveal that the ventrolateral prefrontal cortex plays a causal role in evaluating prior decisions and biasing future decisions.
The expression of the lipoprotein lipase (LPL) transporter GPIHBP1 in glioma capillaries promotes the LPL-mediated processing of triglyceride-rich lipoproteins, thereby providing lipid nutrients for glioma cells.
Slow presynaptic depression in olfactory receptor neurons rescales combinatorial odor representations in postsynaptic neurons and mediates the encoding of stimulus mean and variance.
Functional identification of GABAergic neurons in the ventral tegmental area as a important neuronal subpopulation regulating non-rapid eye movement (NREM) sleep in mice.
Elizabeth Ann Hambleton, Victor Arnold Shivas Jones ... Annika Guse
Diversification of a conserved cholesterol binder drives functional replacement of cholesterol with symbiont-produced sterols in corals living in nutrient-poor environments.
Samuel Frederick Mock Hart, Jose Mario Bello Pineda ... Wenying Shou
Whereas partner-serving phenotype is intuitively quantified as benefit release rate, molecular genetics revealed an example where this thinking fails, motivating a more general metric.
Vincent Guacci, Fiona Chatterjee ... Douglas E Koshland
The interface formed where Smc3p and Mcd1p bind each other regulates cohesin DNA binding and cohesion by a mechanism independently from its putative role as a DNA exit gate.
Chick optic fissure closure is a powerful new model system for epithelial fusion and has revealed Netrin-1 as a conserved and essential mediator of tissue fusion in multiple contexts.
Chicken ANP32A, and not chicken ANP32B, supports influenza polymerase activity and thus editing of this single gene may generate chickens that are resilient to influenza virus infection.
Madison Bolger-Munro, Kate Choi ... Michael R Gold
Arp2/3 complex-mediated actin polymerization shapes how B lymphocytes probe the surface of antigen-presenting cells, promotes coalescence of B cell receptor (BCR) microclusters, amplifies BCR signaling, and enhances B cell activation.
Disi An, Ryosuke Fujiki ... Esteban Orlando Mazzoni
Stem cell-derived motor neurons with differential ALS vulnerability identified proteasome activity as a possible mechanism that explains their differential sensitivity.
Irina L Rempel, Matthew M Crane ... Liesbeth M Veenhoff
In replicative ageing yeast cells, an age-dependent impediment in proper assembly of nuclear pore complexes is associated with altered nuclear transport.
