Featured
-
-
Article
| Open AccessStructure and Scm3-mediated assembly of budding yeast centromeric nucleosomes
There is debate about the structural organization of the yeast centromeric nucleosome and the role of the nonhistone protein Scm3 in its assembly. Dechassaet al.find that yeast centromeric nucleosomes organize DNA in a left-handed superhelix, and show that Scm3 is a specific nucleosome assembly factor.
- Mekonnen Lemma Dechassa
- , Katharina Wyns
- & Karolin Luger
-
Article
| Open AccessTranscription factor IRF8 directs a silencing programme for TH17 cell differentiation
The molecular mechanisms that regulate TH17 cell diversity are poorly understood. Ouyang et al. show that the transcription factor interferon regulatory factor-8 is required for TH17-cell differentiation and that its absence increases the severity of an experimental model of colitis.
- Xinshou Ouyang
- , Ruihua Zhang
- & Huabao Xiong
-
Article
| Open AccessIKKβ regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways
IKK kinases activate nuclear factor-κB, and the activated form of this transcription factor is found in endothelial cells in diseased tissue. In this study, mice lacking IKKβ in the endothelium are generated, and it is shown that defects in endothelial cell function are both IKK kinase activity dependent and independent.
- Noboru Ashida
- , Sucharita SenBanerjee
- & Anthony Rosenzweig
-
Article
| Open AccessAurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis
Mitotic exit is controlled by a cell division checkpoint that prevents premature degradation of cyclin B by the anaphase-promoting complex. Saurinet al. show that Aurora B directly regulates timely establishment of this checkpoint by facilitating activation of Mps1 kinase at unattached kinetochores.
- Adrian T. Saurin
- , Maike S. van der Waal
- & Geert J.P.L. Kops
-
Article
| Open AccessPhotosynthetic growth despite a broken Q-cycle
The Q-cycle is thought to be an essential energetic component of the photosynthetic electron-transfer chain. Here, Chlamydomonas mutants with an inactive Q-cycle but normal levels ofb6fcomplexes are shown to display photosynthetic growth, demonstrating the dispensability of the Q-cycle in the oxygenic photosynthetic chain.
- Alizée Malnoë
- , Francis-André Wollman
- & Fabrice Rappaport
-
Article |
An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation
TheIrx genes are arranged in clusters and the reason for this arrangement is unclear. Using a chromatin conformation capture assay, the authors show that Irx genes share enhancer elements, suggesting that the gene cluster is required for coregulation of the Irxgenes.
- Juan J. Tena
- , M. Eva Alonso
- & José Luis Gómez-Skarmeta
-
Article |
Two splice variants of the IDD14 transcription factor competitively form nonfunctional heterodimers which may regulate starch metabolism
The alternative splicing of genes increases the number and diversity of proteins produced within a cell. Seoet al. demonstrate that the beta form of the alternatively spliced Arabidopsis gene, IDD14, is produced under cold conditions and may have a role in regulating starch accumulation.
- Pil Joon Seo
- , Mi Jung Kim
- & Chung-Mo Park
-
Article |
Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes
The detailed interactions of membrane proteins with their lipid environment are poorly understood. Sonntaget al. use low-resolution X-ray crystallographic data and molecular dynamics simulations to study the manner in which the sarcoendoplasmic reticulum Ca2+–ATPase adapts to different membrane environments.
- Yonathan Sonntag
- , Maria Musgaard
- & Lea Thøgersen
-
Article |
α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
PTEN is a phosphatase that regulates the phosphatidylinositol-3 kinase signalling pathway and is inactivated in many tumour types. Heet al.show that a mannosidase, α-mannosidase 2C1, can inactivate PTEN in prostate cancer cells, and that PTEN-positive human prostate tumours overexpress α-mannosidase 2C1.
- Lizhi He
- , Catherine Fan
- & Damu Tang
-
Article |
Two-dimensional enzyme diffusion in laterally confined DNA monolayers
Little is known about the effects of molecular crowding and confinement on biomolecule function. Castronovoet al. investigate the reactions of restriction enzymes with DNA confined in bushy matrices and find that the enzymes enter at the side of the matrix before diffusing two-dimensionally.
- Matteo Castronovo
- , Agnese Lucesoli
- & Giacinto Scoles
-
Article |
Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors
N-methyl-D-aspartate receptors mediate excitatory synaptic transmission, and those containing GluN2D subunits have an unusually long deactivation time. Vance et al. show that the conformational variability of the ligand-binding domain and the structure of the activating ligand influence deactivation time.
- Katie M. Vance
- , Noriko Simorowski
- & Hiro Furukawa
-
Article
| Open AccessRespiratory distress and perinatal lethality in Nedd4-2-deficient mice
In vitrostudies have suggested that the ubiquitin ligase, Nedd4-2, regulates several proteins, including the epithelial sodium channel. Here by examining Nedd4-2-deficient mice, the authors demonstrate that Nedd4-2 is essential for epithelial sodium channel regulation, fetal and postnatal lung function and animal survival.
- Natasha A. Boase
- , Grigori Y. Rychkov
- & Sharad Kumar
-
Article |
LTD is a protein required for sorting light-harvesting chlorophyll-binding proteins to the chloroplast SRP pathway
Chloroplast proteins are synthesized in the cytosol and imported into the chloroplast before being delivered to the thylakoids. The authors report that an ankyrin-repeat protein, LTD, is essential for the routing of chlorophyll-binding proteins to the signal recognition particle pathway.
- Min Ouyang
- , Xiaoyi Li
- & Lixin Zhang
-
Article
| Open AccessAnnexin-A5 assembled into two-dimensional arrays promotes cell membrane repair
Eukaryotic cell plasma membranes possess a mechanism to repair tears caused by stimuli such as mechanical stress. The authors demonstrate that annexin-A5, when assembled into two-dimensional arrays in the presence of calcium, is required for membrane repair.
- Anthony Bouter
- , Céline Gounou
- & Alain R. Brisson
-
Article |
Adhesive water networks facilitate binding of protein interfaces
The formation of hydrophilic protein–protein interactions cannot be explained by charge–charge interactions. Here, molecular simulations reveal that water forms an adhesive hydrogen-bonded network between proteins, stabilizing intermediate states before the bound complex forms.
- Mazen Ahmad
- , Wei Gu
- & Volkhard Helms
-
Article |
The acetylation of tau inhibits its function and promotes pathological tau aggregation
Phosphorylation of the microtubule-associated protein tau is associated with disease, but other post-translational modifications of tau are not well studied. Here, Cohenet al. study the acetylation of tau and suggest that this form of the protein may be associated with tauopathies.
- Todd J. Cohen
- , Jing L. Guo
- & Virginia M. Y. Lee
-
Article
| Open AccessLipid-dependent gating of a voltage-gated potassium channel
Lipid phosphodiesters affect the conformation of certain potassium channels, but the details of the lipid-channel interactions are unclear. Here, the KvAP channel is found to switch from an active to a resting state when the channels are transferred from a phospholipid membrane to a bilayer lacking phosphodiesters.
- Hui Zheng
- , Weiran Liu
- & Qiu-Xing Jiang
-
Article
| Open AccessErrors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings
Voltage-activated ion channels can be measured in neurons using the cell-attached patch-clamp technique. Williams and Wozny show that this technique is prone to errors that are caused by the flow of current through the ion channels; a method to correct for these discrepancies is described.
- Stephen R. Williams
- & Christian Wozny
-
Article
| Open AccessThe structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CXXC domain proteins bind to CpG DNA sequences and influence chromatin modification. Xuet al.report crystal structures of the CXXC protein CFP1, a component of the SETD1 histone H3K4 methyl transferase complex, and study the molecular mechanisms of DNA-binding specificity.
- Chao Xu
- , Chuanbing Bian
- & Jinrong Min
-
Article
| Open AccessStructural basis for the recognition and cleavage of histone H3 by cathepsin L
Cathepsin L mediates proteolysis of the histone H3 tail and is a factor in cell-cycle progression and cellular differentiation. Adams-Cioabaet al. report crystal structures of an inactive mutant of the protease complexed with substrate peptides, and find that it is highly accommodating of modified substrates.
- Melanie A. Adams-Cioaba
- , Joanne C. Krupa
- & Jinrong Min
-
Article |
A bacterial proteorhodopsin proton pump in marine eukaryotes
Proteorhodopsin is used by prokaryotes to generate energy from light. In this study, the authors describe a prokaryote-to-eukaryote horizontal gene transfer of a bacterial proteorhodopsin gene to dinoflagellates, suggesting that these eukaryotes can also use proteorhodopsin to obtain light and produce energy.
- Claudio H. Slamovits
- , Noriko Okamoto
- & Patrick J. Keeling
-
Article |
Rad23 escapes degradation because it lacks a proteasome initiation region
Rad23 accompanies ubiquitinated substrates to the proteasome for destruction but manages to avoid degradation. In this study, Fishbainet al.show that Rad23 escapes because it lacks an effective initiation region; therefore, the proteasome is unable to engage the protein and unfold it.
- Susan Fishbain
- , Sumit Prakash
- & Andreas Matouschek
-
Article
| Open AccessC-terminal UBA domains protect ubiquitin receptors by preventing initiation of protein degradation
Rad23 and Dsk2 bind polyubiquitylated proteins and escort them to the proteasome for destruction. In this study, Heinenet al.investigate the molecular mechanisms that protect the C-terminal UBA domains of Rad23 and Dsk2 from proteasomal destruction.
- Christian Heinen
- , Klàra Ács
- & Nico P. Dantuma
-
Article |
ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA
Uridines at the wobble position of transfer RNA anticodons are usually modified to allow efficient decoding of messenger RNA codons. In this study, ALKBH8 is shown to be a bifunctional transfer RNA modification enzyme required for the formation of a novel diastereomeric pair of modified wobble uridines.
- Erwin van den Born
- , Cathrine B. Vågbø
- & Pål Ø. Falnes
-
Article |
A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa
The CATSPER heteromeric ion channel complex is required for male fertility and six protein components of the complex have been identified. In this study, the authors identify a seventh gene, CATSPERδ, which is necessary for functional CatSper channels and hyperactivated sperm motility.
- Jean-Ju Chung
- , Betsy Navarro
- & David E. Clapham
-
Article
| Open AccessConformational rearrangement of gastric H+,K+-ATPase induced by an acid suppressant
The gastric proton pump, H+,K+-ATPase, contributes to stomach acidification and is a target of acid suppressants. Here, the three-dimensional structure of the pump is determined using electron crystallography, providing the first structural information about the binding of a new class of acid suppressants.
- Kazuhiro Abe
- , Kazutoshi Tani
- & Yoshinori Fujiyoshi
-
Article
| Open AccessCrystallographic observation of 'induced fit' in a cryptophane host–guest model system
Cryptophane-A is a prototypical organic host molecule that binds reversibly to neutral guest molecules. Taratulaet al.report X-ray structures of cryptophane-A complexed with a range of host molecules to show that the cryptophane host–guest system exhibits ‘induced fit’.
- Olena Taratula
- , P. Aru Hill
- & Ivan J. Dmochowski
-
Article |
The phospholipase D1 pathway modulates macroautophagy
Macroautophagy involves remodelling of intracellular membranes, but the role of lipids and lipid enzymes in this process is poorly understood. Here, the authors demonstrate that phospholipase D1, an enzyme that catalyses the production of phosphatidic acid, has a modulatory role in the autophagy process in mammalian cells.
- Claudia Dall'Armi
- , Andrés Hurtado-Lorenzo
- & Gilbert Di Paolo
-
Article
| Open AccessSystems-wide temporal proteomic profiling in glucose-starved Bacillus subtilis
Identifying the transcripts and proteins that fluctuate in response to stimuli provides important information for understanding cell physiology. In this study, 52% of theBacillus subtilispredicted proteome is identified following glucose starvation, revealing further insight into protein dynamics at a global scale.
- Andreas Otto
- , Jörg Bernhardt
- & Dörte Becher
-
Article |
High rates of photobiological H2 production by a cyanobacterium under aerobic conditions
Hydrogen production using photosynthetic bacteria is an appealing energy source, but typically the bacteria require anaerobic conditions. Here, the authors report a wild-type cyanobacterium strain that shows very high rates of hydrogen production under aerobic environmental conditions.
- Anindita Bandyopadhyay
- , Jana Stöckel
- & Himadri B. Pakrasi
-
Article
| Open AccessStretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope
Bacteria express adhesive proteins on their surface that recognize fibronectin. Using a mechanical stretch assay and steered molecular dynamics, Chabriaet al. demonstrate that the binding of a bacterial adhesin to fibronectin is mechanoregulated, suggesting that bacteria can sense tissue fibre stretching.
- Mamta Chabria
- , Samuel Hertig
- & Viola Vogel
-
Article
| Open AccessSubstrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site
γ-Secretase modulators have promise in the treatment of Alzheimer's disease, but their molecular target is uncertain. Here, fluorescence resonance energy transfer is used to determine that the γ-secretase allosteric site is within the γ-secretase complex and that substrate docking is required for modulators to access the site.
- Kengo Uemura
- , Katherine C. Farner
- & Oksana Berezovska
-
Article
| Open AccessDisruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity
Thioredoxin binding protein-2 (TBP-2) mutant mice have abnormal insulin sensitivity and secretion. In this study, TBP-2-null obese mice are shown to have improved insulin sensitivity and glucose intolerance, suggesting a potential role for TBP-2 inhibition in diabetes treatment.
- Eiji Yoshihara
- , Shimpei Fujimoto
- & Hiroshi Masutani
-
Article |
Overlap between folding and functional energy landscapes for adenylate kinase conformational change
Enzyme function is often dependent on fluctuations between inactive and active states. Olsson and Wolf-Watz show that switching between the inactive and active states of adenylate kinase is associated with partial unfolding/refolding of the enzyme.
- Ulrika Olsson
- & Magnus Wolf-Watz
-
Article
| Open AccessNovel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase
The influenza virus life cycle relies on sialidases, which are classified as group-1 or group-2, depending on the flexibility of the '150-loop'. In this study, chemical compounds are developed, which lock open the '150-loop', selectively inhibiting the activity of group-1 sialidases.
- Santosh Rudrawar
- , Jeffrey C. Dyason
- & Mark von Itzstein
-
Article |
The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation
Superantigens are bacterial toxins that interact with host immunoreceptors. Salineet al.report the X-ray structure of staphylococcal enterotoxin H in complex with its human receptors, MHC class II and the T-cell receptor, providing new insights into superantigenic T-cell activation.
- Maria Saline
- , Karin E. J. Rödström
- & Karin Lindkvist-Petersson
-
Article
| Open AccessTRPM7 is essential for Mg2+ homeostasis in mammals
Magnesium is an essential element of the diet and is a cofactor for many enzymes. In this study, the channel kinase TRPM7 is shown to be essential for magnesium homeostasis, and heterozygous mice lacking the kinase domain show a defect in absorption of magnesium from the diet.
- Lillia V. Ryazanova
- , Lusliany J. Rondon
- & Alexey G. Ryazanov
-
Article
| Open AccessGlobal distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis
Sixty years ago it was suggested that the sickle cell disease mutation survives because the heterozygous genotype confers resistance to malaria, resulting in correlation of the two geographical distributions. The authors use a new global assembly of sickle allele frequencies to support this hypothesis at the global scale.
- Frédéric B. Piel
- , Anand P. Patil
- & Simon I. Hay
-
Article |
A role for TREX components in the release of spliced mRNA from nuclear speckle domains
The pre-mRNA splicing and TREX mRNA export machineries are found in nuclear speckle domains. Diaset al. microinject CMV-DNA constructs into cells and find that transcripts containing functional splice sites accumulate in nuclear speckles and that the TREX complex is required to release the mRNA once processed.
- Anusha P. Dias
- , Kobina Dufu
- & Robin Reed
-
Article |
Protein-binding assays in biological liquids using microscale thermophoresis
Protein interactions in biological environments are expected to differ from the situationin vitro. In this study, a thermophoresis-based technique is described that allows the analysis of protein and small-molecule interactions in biological liquids; the work may allow more efficient drug development.
- Christoph J. Wienken
- , Philipp Baaske
- & Stefan Duhr
-
Article
| Open AccessStructural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly
Frataxin is an essential protein that has been linked to iron–sulphur cluster assembly, and reduced levels are associated with Friedrich's ataxia. In this study, a combination of techniques is used to probe the interactions of the bacterial frataxin orthologue CyaY with the iron–sulphur cluster assembly machinery.
- Filippo Prischi
- , Petr V. Konarev
- & Annalisa Pastore
-
Article |
G-protein β2 subunit interacts with mitofusin 1 to regulate mitochondrial fusion
Little is known about the regulation of mitofusin proteins that are involved in the fusion of mitochondrial membranes. In this study, the authors report that a heterotrimeric G protein, Gβ-subunit 2, can interact with mitofusin 1, and is involved in the regulation of mitochondrial fusion.
- Juan Zhang
- , Weihua Liu
- & Quan Chen
-
Article
| Open AccessFolding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone
Toll-like receptors are involved in pathogen recognition by the innate immune system and rely on the molecular chaperone, gp96, for correct folding. In this article, the chaperone activity of gp96 is shown to be dependent on an additional endoplasmic reticulum protein, CNPY3, for some Toll-like receptors.
- Bei Liu
- , Yi Yang
- & Zihai Li
-
Article |
Biogeography and habitat modelling of high-alpine bacteria
The spatial distribution and parameters that affect soil microorganism communities are largely unknown. In this study, bacterial communities up to 240 metres apart are shown to be similar and are affected by soil pH, plant abundance and snow depth.
- Andrew J. King
- , Kristen R. Freeman
- & Steven K. Schmidt
-
Article |
Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin
Calmodulin is a key mediator of calcium-dependent signalling and is subject to post-translational modifications. Here, evolutionarily conserved methyltransferases are identified which trimethylate Lys-115 of calmodulin, implying a broad role in calcium-dependent signalling.
- Roberta Magnani
- , Lynnette M.A. Dirk
- & Robert L. Houtz
-
Article
| Open AccessPore-opening mechanism in trimeric P2X receptor channels
A recent X-ray structure revealed the closed state of a P2X receptor ion channel. Here, Li and colleagues probe the structural rearrangements that take place during channel opening by measuring the effects of covalent modification of engineered cysteines.
- Mufeng Li
- , Toshimitsu Kawate
- & Kenton J. Swartz
-
Article |
Motion-based DNA detection using catalytic nanomotors
Synthetic nanomotors convert chemical energy into motion. Here, they have been implemented in a motion-based assay that allows specific DNA and ribosomal RNA detection. The technique is fast, simple and sensitive, and the concentration-dependant distance signals of the magnetically aligned nanomotors are detected by optical microscopy.
- Jie Wu
- , Shankar Balasubramanian
- & Joseph Wang
-
Article
| Open AccessDivergent transcriptional activities determine limb identity
The embryonic development of forelimbs and hindlimbs is regulated by transcription factors, including Pitx1, Tbx4 and Tbx5. In this study, the contributions of Tbx4 and Tbx5 to limb identity are further delineated, resulting in the demonstration of a role for Tbx4 in hindlimb skeletal and muscle patterning.
- Jean-François Ouimette
- , Marisol Lavertu Jolin
- & Jacques Drouin
-
Article |
TERRA transcripts are bound by a complex array of RNA-binding proteins
Recent work has revealed that the TTAGGG DNA repeats of telomeres are transcribed to form 'TERRA'. In this study, a set of RNA-binding proteins are shown to bind TERRA transcripts, altering the location of these transcripts at telomeres and regulating telomere abundance and length.
- Isabel López de Silanes
- , Martina Stagno d'Alcontres
- & Maria A Blasco
Browse broader subjects
Browse narrower subjects
- Biocatalysis
- Biogeochemistry
- Bioinorganic chemistry
- Biophysical chemistry
- Carbohydrates
- Chemical modification
- Cytokines
- DNA
- Enzyme mechanisms
- Enzymes
- Glycobiology
- Glycomics
- Histocytochemistry
- Hormones
- Immunochemistry
- Ion channels
- Isoenzymes
- Kinases
- Lipidomics
- Lipids
- Metabolomics
- Metals
- Neurochemistry
- Peptides
- Prions
- Proteases
- Protein folding
- Proteins
- Proteolysis
- Proteomics
- RNA
- Structural biology