The signalling conformation of the insulin receptor ectodomain.

Abstract:

:Understanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy structure of a single insulin bound to a physiologically relevant, high-affinity version of the receptor ectodomain, the latter generated through attachment of C-terminal leucine zipper elements to overcome the conformational flexibility associated with ectodomain truncation. The resolution of the cryo-electron microscopy maps is 3.2 Å in the insulin-binding region and 4.2 Å in the membrane-proximal region. The structure reveals how the membrane proximal domains of the receptor come together to effect signalling and how insulin's negative cooperativity of binding likely arises. Our structure further provides insight into the high affinity of certain super-mitogenic insulins. Together, these findings provide a new platform for insulin analog investigation and design.

journal_name

Nat Commun

journal_title

Nature communications

authors

Weis F,Menting JG,Margetts MB,Chan SJ,Xu Y,Tennagels N,Wohlfart P,Langer T,Müller CW,Dreyer MK,Lawrence MC

doi

10.1038/s41467-018-06826-6

subject

Has Abstract

pub_date

2018-10-24 00:00:00

pages

4420

issue

1

issn

2041-1723

pii

10.1038/s41467-018-06826-6

journal_volume

9

pub_type

杂志文章
  • Nanoporous frameworks exhibiting multiple stimuli responsiveness.

    abstract::Nanoporous frameworks are polymeric materials built from rigid molecules, which give rise to their nanoporous structures with applications in gas sorption and storage, catalysis and others. Conceptually new applications could emerge, should these beneficial properties be manipulated by external stimuli in a reversible...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4588

    authors: Kundu PK,Olsen GL,Kiss V,Klajn R

    更新日期:2014-04-07 00:00:00

  • Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells.

    abstract::Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we investigate the critical functions of CDK4/6-cyclin D kinases, starting from an unbia...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6906

    authors: The I,Ruijtenberg S,Bouchet BP,Cristobal A,Prinsen MB,van Mourik T,Koreth J,Xu H,Heck AJ,Akhmanova A,Cuppen E,Boxem M,Muñoz J,van den Heuvel S

    更新日期:2015-01-06 00:00:00

  • Conformational flexibility and changes underlying activation of the SUMO-specific protease SENP1 by remote substrate binding.

    abstract::Ubiquitin-like (Ubl) modifications regulate nearly all cellular functions in eukaryotes with the largest superfamily of Ubl-specific proteases being Cys proteases. SENP1 is a model for this protease family and responsible for processing SUMO. Here using nuclear magnetic resonance relaxation measurements, chemical shif...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5968

    authors: Chen CH,Namanja AT,Chen Y

    更新日期:2014-09-29 00:00:00

  • Distinct prefrontal top-down circuits differentially modulate sensorimotor behavior.

    abstract::Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Modulation by the prefrontal cortex (PFC) is thought to be key for both processes, but the precise role of specific circuits remains unclear. We examined th...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19772-z

    authors: Huda R,Sipe GO,Breton-Provencher V,Cruz KG,Pho GN,Adam E,Gunter LM,Sullins A,Wickersham IR,Sur M

    更新日期:2020-11-26 00:00:00

  • Spiracular air breathing in polypterid fishes and its implications for aerial respiration in stem tetrapods.

    abstract::The polypterids (bichirs and ropefish) are extant basal actinopterygian (ray-finned) fishes that breathe air and share similarities with extant lobe-finned sarcopterygians (lungfishes and tetrapods) in lung structure. They are also similar to some fossil sarcopterygians, including stem tetrapods, in having large paire...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4022

    authors: Graham JB,Wegner NC,Miller LA,Jew CJ,Lai NC,Berquist RM,Frank LR,Long JA

    更新日期:2014-01-01 00:00:00

  • The Arabidopsis NOT4A E3 ligase promotes PGR3 expression and regulates chloroplast translation.

    abstract::Chloroplast function requires the coordinated action of nuclear- and chloroplast-derived proteins, including several hundred nuclear-encoded pentatricopeptide repeat (PPR) proteins that regulate plastid mRNA metabolism. Despite their large number and importance, regulatory mechanisms controlling PPR expression are poo...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20506-4

    authors: Bailey M,Ivanauskaite A,Grimmer J,Akintewe O,Payne AC,Osborne R,Labandera AM,Etherington RD,Rantala M,Baginsky S,Mulo P,Gibbs DJ

    更新日期:2021-01-11 00:00:00

  • Author Correction: Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41467-020-17712-5

    authors: Zheng J,Fan R,Wu H,Yao H,Yan Y,Liu J,Ran L,Sun Z,Yi L,Dang L,Gan P,Zheng P,Yang T,Zhang Y,Tang T,Wang Y

    更新日期:2020-07-27 00:00:00

  • Mass spectrometry and Monte Carlo method mapping of nanoparticle ligand shell morphology.

    abstract::Janus, patchy, stripe-like, or random arrangements of molecules within the ligand shell of nanoparticles affect many properties. Among all existing ligand shell morphology characterization methods, the one based on mass spectroscopy is arguably the simplest. Its greatest limitation is that the results are qualitative....

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06939-y

    authors: Luo Z,Zhao Y,Darwish T,Wang Y,Hou J,Stellacci F

    更新日期:2018-10-26 00:00:00

  • Myths and reality of HPbI3 in halide perovskite solar cells.

    abstract::All-inorganic perovskites have a special place in halide perovskite family because of their potential for better stability. However, the representative cesium lead iodide (CsPbI3) is metastable and spontaneously converts to the non-perovskite structure at room temperature. Here, we demonstrate that what appears to be ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07204-y

    authors: Ke W,Spanopoulos I,Stoumpos CC,Kanatzidis MG

    更新日期:2018-11-14 00:00:00

  • Switching of band inversion and topological surface states by charge density wave.

    abstract::Topologically nontrivial materials host protected edge states associated with the bulk band inversion through the bulk-edge correspondence. Manipulating such edge states is highly desired for developing new functions and devices practically using their dissipation-less nature and spin-momentum locking. Here we introdu...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-16290-w

    authors: Mitsuishi N,Sugita Y,Bahramy MS,Kamitani M,Sonobe T,Sakano M,Shimojima T,Takahashi H,Sakai H,Horiba K,Kumigashira H,Taguchi K,Miyamoto K,Okuda T,Ishiwata S,Motome Y,Ishizaka K

    更新日期:2020-05-18 00:00:00

  • Dehydrative π-extension to nanographenes with zig-zag edges.

    abstract::Zig-zag nanographenes are promising candidates for the applications in organic electronics due to the electronic properties induced by their periphery. However, the synthetic access to these compounds remains virtually unexplored. There is a lack in efficient and mild strategies origins in the reduced stability, incre...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07095-z

    authors: Lungerich D,Papaianina O,Feofanov M,Liu J,Devarajulu M,Troyanov SI,Maier S,Amsharov K

    更新日期:2018-11-12 00:00:00

  • The conserved microRNA miR-34 regulates synaptogenesis via coordination of distinct mechanisms in presynaptic and postsynaptic cells.

    abstract::Micro(mi)RNA-based post-transcriptional regulatory mechanisms have been broadly implicated in the assembly and modulation of synaptic connections required to shape neural circuits, however, relatively few specific miRNAs have been identified that control synapse formation. Using a conditional transgenic toolkit for co...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-14761-8

    authors: McNeill EM,Warinner C,Alkins S,Taylor A,Heggeness H,DeLuca TF,Fulga TA,Wall DP,Griffith LC,Van Vactor D

    更新日期:2020-02-27 00:00:00

  • Characterization of a membrane-bound C-glucosyltransferase responsible for carminic acid biosynthesis in Dactylopius coccus Costa.

    abstract::Carminic acid, a glucosylated anthraquinone found in scale insects like Dactylopius coccus, has since ancient times been used as a red colorant in various applications. Here we show that a membrane-bound C-glucosyltransferase, isolated from D. coccus and designated DcUGT2, catalyzes the glucosylation of flavokermesic ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02031-z

    authors: Kannangara R,Siukstaite L,Borch-Jensen J,Madsen B,Kongstad KT,Staerk D,Bennedsen M,Okkels FT,Rasmussen SA,Larsen TO,Frandsen RJN,Møller BL

    更新日期:2017-12-07 00:00:00

  • Light-tuned selective photosynthesis of azo- and azoxy-aromatics using graphitic C3N4.

    abstract::Solar-driven photocatalysis has attracted significant attention in water splitting, CO2 reduction and organic synthesis. The syntheses of valuable azo- and azoxyaromatic dyes via selective photoreduction of nitroaromatic compounds have been realised using supported plasmonic metal nanoparticles at elevated temperature...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02527-8

    authors: Dai Y,Li C,Shen Y,Lim T,Xu J,Li Y,Niemantsverdriet H,Besenbacher F,Lock N,Su R

    更新日期:2018-01-04 00:00:00

  • A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction.

    abstract::Loss of protein and organelle quality control secondary to reduced autophagy is a hallmark of aging. However, the physiologic and molecular regulation of autophagy in long-lived organisms remains incompletely understood. Here we show that the Kruppel-like family of transcription factors are important regulators of aut...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00899-5

    authors: Hsieh PN,Zhou G,Yuan Y,Zhang R,Prosdocimo DA,Sangwung P,Borton AH,Boriushkin E,Hamik A,Fujioka H,Fealy CE,Kirwan JP,Peters M,Lu Y,Liao X,Ramírez-Bergeron D,Feng Z,Jain MK

    更新日期:2017-10-13 00:00:00

  • Ontogenetic asymmetry modulates population biomass production and response to harvest.

    abstract::Patterns in biomass production are determined by resource input (productivity) and trophic transfer efficiency. At fixed resource input, variation in consumer biomass production has been related to food quality, metabolic type and diversity among species. In contrast, intraspecific variation in individual body size be...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7441

    authors: Reichstein B,Persson L,De Roos AM

    更新日期:2015-03-04 00:00:00

  • Continuous-variable geometric phase and its manipulation for quantum computation in a superconducting circuit.

    abstract::Geometric phase, associated with holonomy transformation in quantum state space, is an important quantum-mechanical effect. Besides fundamental interest, this effect has practical applications, among which geometric quantum computation is a paradigm, where quantum logic operations are realized through geometric phase ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01156-5

    authors: Song C,Zheng SB,Zhang P,Xu K,Zhang L,Guo Q,Liu W,Xu D,Deng H,Huang K,Zheng D,Zhu X,Wang H

    更新日期:2017-10-20 00:00:00

  • A light-driven three-dimensional plasmonic nanosystem that translates molecular motion into reversible chiroptical function.

    abstract::Nature has developed striking light-powered proteins such as bacteriorhodopsin, which can convert light energy into conformational changes for biological functions. Such natural machines are a great source of inspiration for creation of their synthetic analogues. However, synthetic molecular machines typically operate...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10591

    authors: Kuzyk A,Yang Y,Duan X,Stoll S,Govorov AO,Sugiyama H,Endo M,Liu N

    更新日期:2016-02-02 00:00:00

  • Telomere damage induces internal loops that generate telomeric circles.

    abstract::Extrachromosomal telomeric circles are commonly invoked as important players in telomere maintenance, but their origin has remained elusive. Using electron microscopy analysis on purified telomeres we show that, apart from known structures, telomeric repeats accumulate internal loops (i-loops) that occur in the proxim...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19139-4

    authors: Mazzucco G,Huda A,Galli M,Piccini D,Giannattasio M,Pessina F,Doksani Y

    更新日期:2020-10-20 00:00:00

  • Atomic dispensers for thermoplasmonic control of alkali vapor pressure in quantum optical applications.

    abstract::Alkali metal vapors enable access to single electron systems, suitable for demonstrating fundamental light-matter interactions and promising for quantum logic operations, storage and sensing. However, progress is hampered by the need for robust and repeatable control over the atomic vapor density and over the associat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10158-4

    authors: Rusimova KR,Slavov D,Pradaux-Caggiano F,Collins JT,Gordeev SN,Carbery DR,Wadsworth WJ,Mosley PJ,Valev VK

    更新日期:2019-05-24 00:00:00

  • Evolutionary and functional impact of common polymorphic inversions in the human genome.

    abstract::Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. Here, we develop a new high-throughput genotyping method based...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12173-x

    authors: Giner-Delgado C,Villatoro S,Lerga-Jaso J,Gayà-Vidal M,Oliva M,Castellano D,Pantano L,Bitarello BD,Izquierdo D,Noguera I,Olalde I,Delprat A,Blancher A,Lalueza-Fox C,Esko T,O'Reilly PF,Andrés AM,Ferretti L,Puig M,Cáce

    更新日期:2019-09-17 00:00:00

  • Herbivorous turtle ants obtain essential nutrients from a conserved nitrogen-recycling gut microbiome.

    abstract::Nitrogen acquisition is a major challenge for herbivorous animals, and the repeated origins of herbivory across the ants have raised expectations that nutritional symbionts have shaped their diversification. Direct evidence for N provisioning by internally housed symbionts is rare in animals; among the ants, it has be...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03357-y

    authors: Hu Y,Sanders JG,Łukasik P,D'Amelio CL,Millar JS,Vann DR,Lan Y,Newton JA,Schotanus M,Kronauer DJC,Pierce NE,Moreau CS,Wertz JT,Engel P,Russell JA

    更新日期:2018-03-06 00:00:00

  • SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression.

    abstract::Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female p...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06459-9

    authors: Vazquez MJ,Toro CA,Castellano JM,Ruiz-Pino F,Roa J,Beiroa D,Heras V,Velasco I,Dieguez C,Pinilla L,Gaytan F,Nogueiras R,Bosch MA,Rønnekleiv OK,Lomniczi A,Ojeda SR,Tena-Sempere M

    更新日期:2018-10-10 00:00:00

  • Three-dimensional self-assembled photonic crystals with high temperature stability for thermal emission modification.

    abstract::Selective thermal emission in a useful range of energies from a material operating at high temperatures is required for effective solar thermophotovoltaic energy conversion. Three-dimensional metallic photonic crystals can exhibit spectral emissivity that is modified compared with the emissivity of unstructured metals...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3630

    authors: Arpin KA,Losego MD,Cloud AN,Ning H,Mallek J,Sergeant NP,Zhu L,Yu Z,Kalanyan B,Parsons GN,Girolami GS,Abelson JR,Fan S,Braun PV

    更新日期:2013-01-01 00:00:00

  • A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay.

    abstract::Nonsense-mediated decay (NMD) eliminates transcripts with premature termination codons. Although NMD-induced loss-of-function has been shown to contribute to the genesis of particular cancers, its global functional consequence in tumours has not been characterized. Here we develop an algorithm to predict NMD and apply...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15943

    authors: Hu Z,Yau C,Ahmed AA

    更新日期:2017-06-26 00:00:00

  • Dissecting the role of aberrant DNA methylation in human leukaemia.

    abstract::Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8091

    authors: Amabile G,Di Ruscio A,Müller F,Welner RS,Yang H,Ebralidze AK,Zhang H,Levantini E,Qi L,Martinelli G,Brummelkamp T,Le Beau MM,Figueroa ME,Bock C,Tenen DG

    更新日期:2015-05-22 00:00:00

  • A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

    abstract::Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms11320

    authors: Karlas A,Berre S,Couderc T,Varjak M,Braun P,Meyer M,Gangneux N,Karo-Astover L,Weege F,Raftery M,Schönrich G,Klemm U,Wurzlbauer A,Bracher F,Merits A,Meyer TF,Lecuit M

    更新日期:2016-05-12 00:00:00

  • CMOS-based carbon nanotube pass-transistor logic integrated circuits.

    abstract::Field-effect transistors based on carbon nanotubes have been shown to be faster and less energy consuming than their silicon counterparts. However, ensuring these advantages are maintained for integrated circuits is a challenge. Here we demonstrate that a significant reduction in the use of field-effect transistors ca...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1682

    authors: Ding L,Zhang Z,Liang S,Pei T,Wang S,Li Y,Zhou W,Liu J,Peng LM

    更新日期:2012-02-14 00:00:00

  • Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting.

    abstract::Stem cell transplantation is a promising strategy for therapeutic cardiac regeneration, but current therapies are limited by inefficient interaction between potentially beneficial cells (either exogenously transplanted or endogenously recruited) and the injured tissue. Here we apply targeted nanomedicine to achieve in...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5880

    authors: Cheng K,Shen D,Hensley MT,Middleton R,Sun B,Liu W,De Couto G,Marbán E

    更新日期:2014-09-10 00:00:00

  • Familial Alzheimer's mutations within APPTM increase Aβ42 production by enhancing accessibility of ε-cleavage site.

    abstract::The high Aβ42/Aβ40 production ratio is a hallmark of familial Alzheimer's disease, which can be caused by mutations in the amyloid precursor protein (APP). The C-terminus of Aβ is generated by γ-secretase cleavage within the transmembrane domain of APP (APPTM), a process that is primed by an initial ε-cleavage at eith...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4037

    authors: Chen W,Gamache E,Rosenman DJ,Xie J,Lopez MM,Li YM,Wang C

    更新日期:2014-01-01 00:00:00