Featured
-
-
Article |
Optical measurements of long-range protein vibrations
Many biological processes rely on fluctuations in protein structure, but the characterization of extended structural motions is challenging. Here the authors use orientation-sensitive terahertz near-field microscopy to report the optical observation of long-range protein vibrational modes.
- Gheorghe Acbas
- , Katherine A. Niessen
- & A.G. Markelz
-
Article
| Open AccessIntegrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages
The signalling pathways that confer differences in the responses of dendritic cells and macrophages to LPS remain poorly understood. Here, Ling et al.report that the integrin C11b is required for LPS-induced TLR4 trafficking and signalling in dendritic cells but not in macrophages.
- Guang Sheng Ling
- , Jason Bennett
- & Marina Botto
-
Article |
Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation
Asthma is often characterized by Th2-mediated inflammatory responses, which are initiated by lung dendritic cells. Here, Williams et al.demonstrate that dendritic cell expression of transcription factor IRF4 drives Th2 differentiation through IL-33 and IL-10 activation.
- Jesse W. Williams
- , Melissa Y. Tjota
- & Anne I. Sperling
-
Article |
Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth
Glioblastoma cancers contain brain tumour-initiating cells and targeting these specific cells is an attractive opportunity for therapy. In this study, the authors show that FOXG1 and Groucho/TLE transcription factors are important for glioblastoma growth and might be useful therapeutic targets.
- Federica Verginelli
- , Alessandro Perin
- & Stefano Stifani
-
Article |
TCTP directly regulates ATM activity to control genome stability and organ development in Drosophila melanogaster
Human TCTP, a highly conserved protein linked to tumorigenesis, has been implicated in the cellular DNA damage response in an ATM kinase-dependent manner. Here, Hong et al. demonstrate in vivo that DrosophiladTCTP controls genome stability by enhancing dATM activity towards its substrate H2Av.
- Sung-Tae Hong
- & Kwang-Wook Choi
-
Article |
Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling
The Wnt receptor Frizzled binds its endogenous ligand via a cysteine-rich domain; however, the function of the equivalent domain in Smoothened, a mediator of Hedgehog signalling, is unknown. Rana et al.present the NMR solution structure of this domain, and characterize its interaction with the glucocorticoid budesonide.
- Rajashree Rana
- , Candace E. Carroll
- & Jie J. Zheng
-
Article |
Functional anatomy of an allosteric protein
ϕ analysis provides a means to tease apart the dynamics of fast conformational changes in proteins by analysing the thermodynamic impact of point mutations. Purohit et al.apply this approach on a grand scale to map energy changes associated with the opening and closing of an acetylcholine receptor.
- Prasad Purohit
- , Shaweta Gupta
- & Anthony Auerbach
-
Article |
A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development
The establishment of a memory phenotype in T cells requires profound changes in their transcriptional profile, but many components of this profile are still not known. Here, the authors perform a systematic study to identify key transcription factors associated with memory CD8+T-cell development.
- Guangan Hu
- & Jianzhu Chen
-
Article
| Open AccessKaiC intersubunit communication facilitates robustness of circadian rhythms in cyanobacteria
The cyanobacterial circadian oscillator comprises an autoregulatory loop that is driven by phosphorylation and dephosphorylation of the hexameric kinase KaiC. Kitayama et al.reveal how interactions between KaiC subunits regulate its catalytic activities and ensure robust circadian behaviour.
- Yohko Kitayama
- , Taeko Nishiwaki-Ohkawa
- & Takao Kondo
-
Article |
The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans
The Caenorhabditis elegans neuropeptide NLP-22 is regulated by a larval circadian clock that is similar to circadian clocks in mammals. Nelson et al. show that NLP-22, expressed in Caenorhabditis elegansRIA interneurons, regulates a sleep-like behavioural quiescence.
- M.D. Nelson
- , N.F. Trojanowski
- & D.M. Raizen
-
Article |
Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer
Whether microRNA processing mediated by Dicer is regulated in a cell-cycle-dependent manner is unknown. Here, Chen et al.show that Cyclin D1, which is important in the control of the cell cycle, regulates the expression of Dicer, and that Cyclin D1 and Dicer expression levels correlate in breast cancer.
- Zuoren Yu
- , Liping Wang
- & Richard G. Pestell
-
Article |
Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes
The transcription factor Sox9 together with its co-regulators promotes chondrocyte differentiation. Here Hata et al.find that Arid5b acts as a transcriptional co-regulator of Sox9 by regulating histone demethylation of Sox9 target genes during chondrogenesis in mice.
- Kenji Hata
- , Rikako Takashima
- & Toshiyuki Yoneda
-
Article
| Open AccessVisualization and targeted disruption of protein interactions in living cells
Screens for protein–protein interactions and for drugs that disrupt them typically use in vitro assays which fail to capture the complexity of the cell’s interior. By fixing proteins to distinct cellular locations, Herce et al.demonstrate a fluorescent-three-hybrid approach to probe such interactions in their cellular contexts.
- Henry D. Herce
- , Wen Deng
- & M. Cristina Cardoso
-
Article |
Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria
The accumulation of superoxide in mitochondria is counteracted by superoxide dismutase 1 and its activating chaperone CCS1. Suzuki et al.show that in human cells, mature CCS1 itself mediates CCS1 import and helps to oxidize CCS1 and SOD1 in the mitochondrial intermembrane space.
- Yutaka Suzuki
- , Muna Ali
- & Jan Riemer
-
Article
| Open Accessp53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1
The protein p53 is an important tumour suppressor. Here Wanget al.show that p53 can induce expression of MHC class I on the cell surface by promoting expression of the aminopeptidase ERAP1, and that this mechanism operates in cancer cells as well as those infected with influenza virus.
- Bei Wang
- , Dandan Niu
- & Ee Chee Ren
-
Article
| Open AccessComplement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration
Components of the complement system have been shown to promote liver regeneration. Haynes et al. demonstrate that the complement fragment C3a can induce regeneration of the embryonic chick retina from stem and progenitor cells of the ciliary margin via activation of STAT3 and other downstream signalling pathways.
- Tracy Haynes
- , Agustin Luz-Madrigal
- & Katia Del Rio-Tsonis
-
Article
| Open AccessEndonuclease V cleaves at inosines in RNA
Bacterial endonuclease V enzymes are characterized as DNA repair proteins. Here the authors show that human endonuclease V is an inosine-specific ribonuclease, indicating a role for this enzyme in normal RNA metabolism rather than DNA repair.
- Erik Sebastian Vik
- , Meh Sameen Nawaz
- & Ingrun Alseth
-
Article
| Open AccessHuman endonuclease V is a ribonuclease specific for inosine-containing RNA
In Escherichia coli, the highly conserved enzyme endonuclease V has a role in DNA repair. Here the authors show that human endonuclease V is an inosine 3' endoribonuclease and that Tudor Staphylococcal nuclease enhances this activity, suggesting a role for human endonuclease V in RNA metabolism.
- Yoko Morita
- , Toshihiro Shibutani
- & Isao Kuraoka
-
Article |
PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine
Tet proteins control DNA demethylation, but how the DNA target regions are determined is unclear. Here the authors report that during adipocyte differentiation, PPARγ binds to the PPAR-response element and recruits Tet proteins, thereby inducing local DNA demethylation.
- Katsunori Fujiki
- , Akihiro Shinoda
- & Masayuki Murata
-
Article |
Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells
Proteins are ideal building blocks for self-assembly of artificial cell-like architectures, but their realization is rare. Huang et al.report an interfacial assembly of protein–polymer conjugates, which exhibit cellular properties such as encapsulating guest molecules and switching enzyme activity.
- Xin Huang
- , Mei Li
- & Stephen Mann
-
Article |
Antagonism between binding site affinity and conformational dynamics tunes alternative cis-interactions within Shp2
Competition between inter- and intra-molecular interactions is a commonly observed property of modular signalling proteins. Here, the authors show that in the phosphatase Shp2, this balance is maintained by a trade-off between binding site affinities and conformational stability.
- Jie Sun
- , Shaoying Lu
- & Yingxiao Wang
-
Article |
Fibroblast growth factor 21 protects against cardiac hypertrophy in mice
Fibroblast growth factor 21 (FGF21) regulates energy metabolism in peripheral tissues. Here Planavila and colleagues show that FGF21 also acts directly on cardiomyocytes, thereby protecting mice against cardiac hypertrophy.
- A. Planavila
- , I. Redondo
- & F. Villarroya
-
Article |
Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides
The expression of specific genes can be controlled by the combination of DNA-binding proteins, which determines their binding site selectivity. Here, simplified synthetic basic region leucine zipper-based peptides are induced to dimerize either through their C- or N-terminus, and thus are targeted to different DNA sequences.
- Jesús Mosquera
- , Adrián Jiménez-Balsa
- & José L Mascareñas
-
Article |
Ribosomal protein S1 functions as a termination factor in RNA synthesis by Qβ phage replicase
Protein S1, a subunit of the Qß phage RNA-directed RNA polymerase, was thought to only initiate copying of the phage RNA plus strand. Here, the authors show that S1 stimulates replication of any cognate template by promoting release of the newly synthesized product strand.
- Nikita N. Vasilyev
- , Zarina S. Kutlubaeva
- & Alexander B. Chetverin
-
Article |
Dynamin−SNARE interactions control trans-SNARE formation in intracellular membrane fusion
Dynamin promotes membrane fission by constricting the neck of invaginating membranes; however, it was recently shown that dynamin also regulates membrane fusion. Here the authors show that this fusogenic activity is mediated by interaction with the Qa SNARE, thereby promoting trans-SNARE formation.
- Kannan Alpadi
- , Aditya Kulkarni
- & Christopher Peters
-
Article |
An engineered dimeric protein pore that spans adjacent lipid bilayers
An important challenge in the bottom-up fabrication of artificial tissues is communication between compartments bounded by lipid bilayers. Mantri et al. engineer a dimeric transmembrane pore that, like eukaryotic gap junctions, can form a conductive pathway between adjacent bilayers.
- Shiksha Mantri
- , K. Tanuj Sapra
- & Hagan Bayley
-
Article |
A new protein complex promoting the assembly of Rad51 filaments
RecA/Rad51 proteins catalyse the recognition and exchange between two homologous DNA strands during homologous recombination. Sasanuma et al. now demonstrate that Rad51 association with ssDNA is mediated by a complex consisting of Psy3, Csm2, Shu1 and Shu2 proteins.
- Hiroyuki Sasanuma
- , Maki S. Tawaramoto
- & Akira Shinohara
-
Article
| Open AccessThe transcriptional repressor NKAP is required for the development of iNKT cells
The transcriptional repressor NKAP is required at an early stage of T cell development for the differentiation of αβ T cells. Thapa et al.now show that at a later stage, NKAP has a specific role in positive selection of double positive thymocytes into the iNKT cell lineage.
- Puspa Thapa
- , Joy Das
- & Virginia Smith Shapiro
-
Article |
COG complexes form spatial landmarks for distinct SNARE complexes
COG complexes are thought to be involved in tethering of intra-Golgi vesicles. Here the authors show that individual COG complex subunits direct the assembly of distinct vesicle-tethering platforms, suggesting that COG subunits have a role in the specificity of vesicular sorting.
- Rose Willett
- , Tetyana Kudlyk
- & Vladimir Lupashin
-
Article |
Ground-state proton transfer in the photoswitching reactions of the fluorescent protein Dronpa
The ‘on’ and ‘off’ states of the photoswitchable protein Dronpa have been characterized, but the interconversion process remains poorly understood. Here the authors perform time-resolved ultrafast infrared measurements to follow both the structural changes and proton transfer events that occur during conversion.
- Mark M. Warren
- , Marius Kaucikas
- & Jasper J. van Thor
-
Article |
Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity
Trichoplaxis the most primitive multicellular animal on Earth and thus provides insight into the earliest stages of evolution. Delving deep into the proteome, Heck and colleagues observe a burst in tyrosine phosphorylation, confirming the hypothesis that at the onset of this new communication system a surplus of phosphorylation took place.
- Jeffrey H. Ringrose
- , Henk W.P. van den Toorn
- & Albert J.R. Heck
-
Article |
Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration
Heat shock factor-1 is a transcriptional regulator of heat shock proteins that is implicated in neurodegeneration. Kondo and colleagues study the effects of deleting heat shock factor-1 in a mouse model of muscular dystrophy and find that this augments the condition via the accumulation of androgen receptors.
- Naohide Kondo
- , Masahisa Katsuno
- & Gen Sobue
-
Article |
hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins
Delivery of lysosome-associated membrane proteins (LAMPs), is important for lysosome stability and function. Here, Pols et al. identify a previously uncharacterized pathway for transport of lysosome-associated membrane proteins LAMPs directly from the trans-golgi network to late endosomes.
- Maaike S. Pols
- , Eline van Meel
- & Judith Klumperman
-
Article
| Open AccessExtracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors
Levels of extracellular calcium can increase at sites of infection and inflammation; however, the physiological significance of this has been unclear. This work shows that extracellular calcium acts as a danger signal, triggering the NLRP3 inflammasome via two G protein-coupled receptors.
- Manuela Rossol
- , Matthias Pierer
- & Ulf Wagner
-
Article
| Open AccessAlba shapes the archaeal genome using a delicate balance of bridging and stiffening the DNA
How the genome is physically organized is less understood in archaea than in eubacteria or eukaryotes. Laurens et al. measure DNA binding by the Sulfolobus solfataricusproteins Alba1 and Alba2 using single-molecule techniques and conclude that the presence of Alba2 leads to more bridging between DNA.
- Niels Laurens
- , Rosalie P.C. Driessen
- & Gijs J.L. Wuite
-
Article
| Open AccessVirus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection
Host–pathogen relationships can be mediated by polyvalent glycan ligand–protein interactions. Here well-defined highly valent glycodendrimeric constructs are synthesized that can mimic pathogens, and can inhibit a model of infection by the Ebola virus.
- Renato Ribeiro-Viana
- , Macarena Sánchez-Navarro
- & Benjamin G. Davis
-
Article
| Open AccessMPIase is a glycolipozyme essential for membrane protein integration
Proteins are integrated into cellular membranes either co-translationally through Sec/SRP or post-translationally by chaperones. These authors show that an integration-dedicated chaperone inE. coli, MPIase, is a glycolipid and facilitates protein insertion into the inner membrane of the bacterium.
- Ken-ichi Nishiyama
- , Masahide Maeda
- & Keiko Shimamoto
-
Article |
Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart
Mice that cannot produce the hormone Klotho show various aging-related phenotypes. Here, Xie and colleagues reveal that Klotho protects the heart of mice from stress-induced remodelling by inhibiting exocytosis of the TRPC6 ion channel in cardiomyocytes.
- Jian Xie
- , Seung-Kuy Cha
- & Chou-Long Huang
-
Article |
The metastasis-promoting S100A4 protein confers neuroprotection in brain injury
Multifunctional S100 proteins are upregulated in brain injury, but their role in neurodegeneration is not clear. Dmytriyeva and colleagues study in vivomodels of brain trauma and find that the S100A4 protein and its peptide mimetics protect neurons via the interleukin-10 receptor and the Janus kinase (JAK)/STAT pathway.
- Oksana Dmytriyeva
- , Stanislava Pankratova
- & Darya Kiryushko
-
Article |
Imaging the post-fusion release and capture of a vesicle membrane protein
Rapid synaptic transmission requires efficient recycling of synaptic vesicle membrane proteins. Sochackiet al.use live cell, electron and super-resolution microscopy to visualize exocytosis of vesicular transporters and their rapid recapture in clathrin-rich microdomains in the plasma membrane.
- Kem A. Sochacki
- , Ben T. Larson
- & Justin W. Taraska
-
Article
| Open AccessEnhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B
HSP70 is a molecular chaperone that aids protein folding. In this study, HSP70 is shown to be methylated and this post-translationally modified protein is elevated in expression in human cancers and promotes the activity of Aurora kinase B.
- Hyun-Soo Cho
- , Tadahiro Shimazu
- & Ryuji Hamamoto
-
Article
| Open AccessGreatwall kinase and cyclin B-Cdk1 are both critical constituents of M-phase-promoting factor
Cyclin B–Cdk1 is thought to be synonymous with the promoting factor that drives entry into M-phase of the cell cycle. Here, Greatwall kinase is shown to be required for the breakdown of the nuclear envelope and the assembly of the spindle on entry into M-phase, suggesting that it too is a part of the M-phase-promoting factor.
- Masatoshi Hara
- , Yusuke Abe
- & Takeo Kishimoto
-
Article
| Open AccessEfficacy of the β2-adrenergic receptor is determined by conformational equilibrium in the transmembrane region
Many drugs exist that target the β-adrenergic receptor, but they have different efficacies. Kofukuet al. use NMR to show that methionine 82 in the transmembrane domain undergoes conformational changes depending on whether agonists or inverse agonists are bound, explaining the differential drug efficacy.
- Yutaka Kofuku
- , Takumi Ueda
- & Ichio Shimada
-
Article
| Open AccessThe allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling
Class A seven transmembrane helical receptors harbour vestibules at the entrance to the ligand-binding domain. Here, Bocket al. use probes to monitor the conformation of the M2 muscarinic receptor and show that the vestibule alters the extent of receptor movement.
- Andreas Bock
- , Nicole Merten
- & Klaus Mohr
-
Article |
Macrophage VLDL receptor promotes PAFAH secretion in mother's milk and suppresses systemic inflammation in nursing neonates
Mother's milk contains a number of protective factors, such as the anti-inflammatory enzyme PAFAH. Here, Duet al. show that the VLDL receptor protects nursing newborns from systemic inflammation by maintaining secretion of PAFAH from maternal macrophages into mother's milk.
- Yang Du
- , Marie Yang
- & Yihong Wan
-
Article |
Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A
The mitochondrial transcription factor A (TFAM) mediates both mitochondrial transcription and DNA compaction, but how it achieves these two functions is unknown. In this study, TFAM is shown to slide along DNA and cause local melting, suggesting a mechanism for how TFAM modulates both transcription and compaction.
- Géraldine Farge
- , Niels Laurens
- & Gijs J.L. Wuite
-
Article
| Open AccessDistinct loops in arrestin differentially regulate ligand binding within the GPCR opsin
Following retinalcis/trans isomerisation, the active form of the G-protein-coupled receptor rhodopsin decays to opsin and all-trans-retinal. In this study, arrestin, a regulator of G-protein-coupled receptor activity, is shown to facilitate the concurrent sequestering of toxic all-trans-retinal and regeneration of 11-cis-retinal within the opsin population.
- Martha E. Sommer
- , Klaus Peter Hofmann
- & Martin Heck
-
Article
| Open AccessProteomic screen reveals Fbw7 as a modulator of the NF-κB pathway
Fbw7 is a ubiquitin-ligase, which targets several oncoproteins for proteolysis, and is therefore important for the control and prevention of tumorigenesis. In this study, Arabi and colleagues carry out a proteomic screen of the targets of Fbw7, and identify Nuclear Factor of κ-B2 as a substrate.
- Azadeh Arabi
- , Karim Ullah
- & Olle Sangfelt
-
Article |
Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains
The peptide sequence of transcription activator-like effectors (TALEs) can be customized to tailor the binding of TALEs to specific DNA sequences. Conget al. improve TALE specificity for guanine binding and use a genetic construct based on TALEs to efficiently repress expression of a target gene.
- Le Cong
- , Ruhong Zhou
- & Feng Zhang
Browse broader subjects
Browse narrower subjects
- Acetyltransferases
- Blood proteins
- Carrier proteins
- Cell-cycle proteins
- Cerebrospinal fluid proteins
- Chaperones
- Chromatin
- Circadian rhythm signalling peptides and proteins
- Colipases
- Complement
- Contractile proteins
- Cytoskeletal proteins
- DNA-binding proteins
- G protein-coupled receptors
- Glycoproteins
- GTP-binding protein regulators
- Integrins
- Intracellular signalling peptides and proteins
- Lectins
- Lipoproteins
- Membrane proteins
- Metalloproteins
- Methylases
- Mitochondrial proteins
- Nuclear receptors
- Nucleases
- Nucleoproteins
- Nucleotide-binding proteins
- Oncogene proteins
- Phosphoproteins
- Phosphorylases
- Proteome
- Ribosomal proteins
- RNA-binding proteins
- Scleroproteins
- Selenium-binding proteins
- Sumoylated proteins
- Thioredoxins
- Transcription factors
- Tumour-suppressor proteins
- Ubiquitins
- Ubiquitylated proteins
- Viral proteins