当前位置： SCI文献检索 > Nature Communications期刊下所有文献 > High-resolution ex vivo NMR spectroscopy of human Z α1-antitrypsin.

High-resolution ex vivo NMR spectroscopy of human Z α1-antitrypsin.

Abstract：

:Genetic mutations predispose the serine protease inhibitor α1-antitrypsin to misfolding and polymerisation within hepatocytes, causing liver disease and chronic obstructive pulmonary disease. This misfolding occurs via a transiently populated intermediate state, but our structural understanding of this process is limited by the instability of recombinant α1-antitrypsin variants in solution. Here we apply NMR spectroscopy to patient-derived samples of α1-antitrypsin at natural isotopic abundance to investigate the consequences of disease-causing mutations, and observe widespread chemical shift perturbations for methyl groups in Z AAT (E342K). By comparison with perturbations induced by binding of a small-molecule inhibitor of misfolding we conclude that they arise from rapid exchange between the native conformation and a well-populated intermediate state. The observation that this intermediate is stabilised by inhibitor binding suggests a paradoxical approach to the targeted treatment of protein misfolding disorders, wherein the stabilisation of disease-associated states provides selectivity while inhibiting further transitions along misfolding pathways.

journal_name

Nat Commun

journal_title

Nature communications

authors

Jagger AM,Waudby CA,Irving JA,Christodoulou J,Lomas DA

doi

10.1038/s41467-020-20147-7

subject

Has Abstract

pub_date

2020-12-11 00:00:00

pages

6371

issue

1

issn

2041-1723

pii

10.1038/s41467-020-20147-7

journal_volume

11

pub_type

杂志文章

相关文献

Nature Communications文献大全
  • Author Correction: Puma genomes from North and South America provide insights into the genomic consequences of inbreeding.

    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： 已发布勘误

    doi：10.1038/s41467-019-13096-3

    authors： Saremi NF,Supple MA,Byrne A,Cahill JA,Coutinho LL,Dalén L,Figueiró HV,Johnson WE,Milne HJ,O'Brien SJ,O'Connell B,Onorato DP,Riley SPD,Sikich JA,Stahler DR,Villela PMS,Vollmers C,Wayne RK,Eizirik E,Corbett-Detig RB,

    更新日期：2019-11-21 00:00:00

  • Shared developmental programme strongly constrains beak shape diversity in songbirds.

    abstract：:The striking diversity of bird beak shapes is an outcome of natural selection, yet the relative importance of the limitations imposed by the process of beak development on generating such variation is unclear. Untangling these factors requires mapping developmental mechanisms over a phylogeny far exceeding model syste...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms4700

    authors： Fritz JA,Brancale J,Tokita M,Burns KJ,Hawkins MB,Abzhanov A,Brenner MP

    更新日期：2014-04-16 00:00:00

  • Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans.

    abstract：:Ribosomes are essential intracellular machines composed of proteins and RNA molecules. The DNA sequences (rDNA) encoding ribosomal RNAs (rRNAs) are tandemly repeated and give origin to the nucleolus. Here we develop a computational method for estimating rDNA dosage (copy number) and mitochondrial DNA abundance using w...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms5850

    authors： Gibbons JG,Branco AT,Yu S,Lemos B

    更新日期：2014-09-11 00:00:00

  • Serial processing of kinematic signals by cerebellar circuitry during voluntary whisking.

    abstract：:Purkinje cells (PCs) in Crus 1 represent whisker movement via linear changes in firing rate, but the circuit mechanisms underlying this coding scheme are unknown. Here we examine the role of upstream inputs to PCs-excitatory granule cells (GCs) and inhibitory molecular layer interneurons-in processing of whisking sign...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-017-00312-1

    authors： Chen S,Augustine GJ,Chadderton P

    更新日期：2017-08-10 00:00:00

  • LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase.

    abstract：:In response to brain injury, microglia rapidly extend processes that isolate lesion sites and protect the brain from further injury. Here we report that microglia carrying a pathogenic mutation in the Parkinson's disease (PD)-associated gene, G2019S-LRRK2 (GS-Tg microglia), show retarded ADP-induced motility and delay...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms9255

    authors： Choi I,Kim B,Byun JW,Baik SH,Huh YH,Kim JH,Mook-Jung I,Song WK,Shin JH,Seo H,Suh YH,Jou I,Park SM,Kang HC,Joe EH

    更新日期：2015-09-14 00:00:00

  • Dynamical observations on the crack tip zone and stress corrosion of two-dimensional MoS2.

    abstract：:Whether and how fracture mechanics needs to be modified for small length scales and in systems of reduced dimensionality remains an open debate. Here, employing in situ transmission electron microscopy, atomic structures and dislocation dynamics in the crack tip zone of a propagating crack in two-dimensional (2D) mono...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms14116

    authors： Ly TH,Zhao J,Cichocka MO,Li LJ,Lee YH

    更新日期：2017-01-18 00:00:00

  • Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress.

    abstract：:A high-sugar diet has been associated with reduced lifespan in organisms ranging from worms to mammals. However, the mechanisms underlying the harmful effects of glucose are poorly understood. Here we establish a causative relationship between endogenous glucose storage in the form of glycogen, resistance to oxidative...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms15868

    authors： Gusarov I,Pani B,Gautier L,Smolentseva O,Eremina S,Shamovsky I,Katkova-Zhukotskaya O,Mironov A,Nudler E

    更新日期：2017-06-19 00:00:00

  • Sensory perception of dead conspecifics induces aversive cues and modulates lifespan through serotonin in Drosophila.

    abstract：:Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. We found that in the vinegar fly, Drosophila melanogaster, exposure to dead conspecifics in the en...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-10285-y

    authors： Chakraborty TS,Gendron CM,Lyu Y,Munneke AS,DeMarco MN,Hoisington ZW,Pletcher SD

    更新日期：2019-05-30 00:00:00

  • Dense GeV electron-positron pairs generated by lasers in near-critical-density plasmas.

    abstract：:Pair production can be triggered by high-intensity lasers via the Breit-Wheeler process. However, the straightforward laser-laser colliding for copious numbers of pair creation requires light intensities several orders of magnitude higher than possible with the ongoing laser facilities. Despite the numerous proposed a...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms13686

    authors： Zhu XL,Yu TP,Sheng ZM,Yin Y,Turcu IC,Pukhov A

    更新日期：2016-12-14 00:00:00

  • AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2.

    abstract：:MicroRNAs (miRNAs) associated with Argonaute proteins (AGOs) regulate gene expression in mammals. miRNA 3' ends are subject to frequent sequence modifications, which have been proposed to affect miRNA stability. However, the underlying mechanism is not well understood. Here, by genetic and biochemical studies as well ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-16533-w

    authors： Yang A,Shao TJ,Bofill-De Ros X,Lian C,Villanueva P,Dai L,Gu S

    更新日期：2020-06-02 00:00:00

  • Lung-derived HMGB1 is detrimental for vascular remodeling of metabolically imbalanced arterial macrophages.

    abstract：:Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, the mechanism underlying the pathological dialogue between the lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence of AAA and accelerates macrophage-driven prote...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-18088-2

    authors： Boytard L,Hadi T,Silvestro M,Qu H,Kumpfbeck A,Sleiman R,Fils KH,Alebrahim D,Boccalatte F,Kugler M,Corsica A,Gelb BE,Jacobowitz G,Miller G,Bellini C,Oakes J,Silvestre JS,Zangi L,Ramkhelawon B

    更新日期：2020-08-27 00:00:00

  • Regulation of PCNA cycling on replicating DNA by RFC and RFC-like complexes.

    abstract：:Replication-Factor-C (RFC) and RFC-like complexes (RLCs) mediate chromatin engagement of the proliferating cell nuclear antigen (PCNA). It remains controversial how RFC and RLCs cooperate to regulate PCNA loading and unloading. Here, we show the distinct PCNA loading or unloading activity of each clamp loader. ATAD5-R...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-10376-w

    authors： Kang MS,Ryu E,Lee SW,Park J,Ha NY,Ra JS,Kim YJ,Kim J,Abdel-Rahman M,Park SH,Lee KY,Kim H,Kang S,Myung K

    更新日期：2019-06-03 00:00:00

  • Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors.

    abstract：:Hydride transfers play a crucial role in a multitude of biological redox reactions and are mediated by flavin, deazaflavin or nicotinamide adenine dinucleotide cofactors at standard redox potentials ranging from 0 to -340 mV. 2-Naphthoyl-CoA reductase, a key enzyme of oxygen-independent bacterial naphthalene degradati...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-10078-3

    authors： Willistein M,Bechtel DF,Müller CS,Demmer U,Heimann L,Kayastha K,Schünemann V,Pierik AJ,Ullmann GM,Ermler U,Boll M

    更新日期：2019-05-06 00:00:00

  • Cascaded spintronic logic with low-dimensional carbon.

    abstract：:Remarkable breakthroughs have established the functionality of graphene and carbon nanotube transistors as replacements to silicon in conventional computing structures, and numerous spintronic logic gates have been presented. However, an efficient cascaded logic structure that exploits electron spin has not yet been d...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms15635

    authors： Friedman JS,Girdhar A,Gelfand RM,Memik G,Mohseni H,Taflove A,Wessels BW,Leburton JP,Sahakian AV

    更新日期：2017-06-05 00:00:00

  • Superconducting metamaterials for waveguide quantum electrodynamics.

    abstract：:Embedding tunable quantum emitters in a photonic bandgap structure enables control of dissipative and dispersive interactions between emitters and their photonic bath. Operation in the transmission band, outside the gap, allows for studying waveguide quantum electrodynamics in the slow-light regime. Alternatively, tun...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-06142-z

    authors： Mirhosseini M,Kim E,Ferreira VS,Kalaee M,Sipahigil A,Keller AJ,Painter O

    更新日期：2018-09-12 00:00:00

  • Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes.

    abstract：:Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies wi...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms13515

    authors： Reuten R,Patel TR,McDougall M,Rama N,Nikodemus D,Gibert B,Delcros JG,Prein C,Meier M,Metzger S,Zhou Z,Kaltenberg J,McKee KK,Bald T,Tüting T,Zigrino P,Djonov V,Bloch W,Clausen-Schaumann H,Poschl E,Yurchenco PD,Eh

    更新日期：2016-11-30 00:00:00

  • Self-cleaning and surface chemical reactions during hafnium dioxide atomic layer deposition on indium arsenide.

    abstract：:Atomic layer deposition (ALD) enables the ultrathin high-quality oxide layers that are central to all modern metal-oxide-semiconductor circuits. Crucial to achieving superior device performance are the chemical reactions during the first deposition cycle, which could ultimately result in atomic-scale perfection of the...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-03855-z

    authors： Timm R,Head AR,Yngman S,Knutsson JV,Hjort M,McKibbin SR,Troian A,Persson O,Urpelainen S,Knudsen J,Schnadt J,Mikkelsen A

    更新日期：2018-04-12 00:00:00

  • An invariability-area relationship sheds new light on the spatial scaling of ecological stability.

    abstract：:The spatial scaling of stability is key to understanding ecological sustainability across scales and the sensitivity of ecosystems to habitat destruction. Here we propose the invariability-area relationship (IAR) as a novel approach to investigate the spatial scaling of stability. The shape and slope of IAR are largel...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms15211

    authors： Wang S,Loreau M,Arnoldi JF,Fang J,Rahman KA,Tao S,de Mazancourt C

    更新日期：2017-05-19 00:00:00

  • A single NaK channel conformation is not enough for non-selective ion conduction.

    abstract：:NaK and other non-selective channels are able to conduct both sodium (Na+) and potassium (K+) with equally high efficiency. In contrast to previous crystallographic results, we show that the selectivity filter (SF) of NaK in native-like lipid membranes adopts two distinct conformations that are stabilized by either Na...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-03179-y

    authors： Shi C,He Y,Hendriks K,de Groot BL,Cai X,Tian C,Lange A,Sun H

    更新日期：2018-02-19 00:00:00

  • Symmetry-protected hierarchy of anomalous multipole topological band gaps in nonsymmorphic metacrystals.

    abstract：:Symmetry and topology are two fundamental aspects of many quantum states of matter. Recently new topological materials, higher-order topological insulators, were discovered, featuring bulk-edge-corner correspondence that goes beyond the conventional topological paradigms. Here we discover experimentally that the nonsy...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-13861-4

    authors： Zhang X,Lin ZK,Wang HX,Xiong Z,Tian Y,Lu MH,Chen YF,Jiang JH

    更新日期：2020-01-03 00:00:00

  • Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer.

    abstract：:Gut microbiota composition influences the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remain unclear. Molecular mechanism whereby gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. Short-chain fatty acids (...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-16079-x

    authors： Coutzac C,Jouniaux JM,Paci A,Schmidt J,Mallardo D,Seck A,Asvatourian V,Cassard L,Saulnier P,Lacroix L,Woerther PL,Vozy A,Naigeon M,Nebot-Bral L,Desbois M,Simeone E,Mateus C,Boselli L,Grivel J,Soularue E,Lepage P,

    更新日期：2020-05-01 00:00:00

  • In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels.

    abstract：:In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms2406

    authors： Sekine H,Shimizu T,Sakaguchi K,Dobashi I,Wada M,Yamato M,Kobayashi E,Umezu M,Okano T

    更新日期：2013-01-01 00:00:00

  • Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference.

    abstract：:The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique-Subtype and Stage Inference (SuStaIn)-able to uncover data-driven...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-05892-0

    authors： Young AL,Marinescu RV,Oxtoby NP,Bocchetta M,Yong K,Firth NC,Cash DM,Thomas DL,Dick KM,Cardoso J,van Swieten J,Borroni B,Galimberti D,Masellis M,Tartaglia MC,Rowe JB,Graff C,Tagliavini F,Frisoni GB,Laforce R Jr,Fin

    更新日期：2018-10-15 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

  • Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens.

    abstract：:Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer antibiotics with novel scaffolds. As historically many commercial drugs were derived from natura...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-05821-1

    authors： Lin Z,Xu X,Zhao S,Yang X,Guo J,Zhang Q,Jing C,Chen S,He Y

    更新日期：2018-09-04 00:00:00

  • Directly visualizing the sign change of d-wave superconducting gap in Bi2Sr2CaCu2O8+δ by phase-referenced quasiparticle interference.

    abstract：:The superconducting state is formed by the condensation of Cooper pairs and protected by the superconducting gap. The pairing interaction between the two electrons of a Cooper pair determines the gap function. Thus, it is pivotal to detect the gap structure for understanding the mechanism of superconductivity. In cupr...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-09340-5

    authors： Gu Q,Wan S,Tang Q,Du Z,Yang H,Wang QH,Zhong R,Wen J,Gu GD,Wen HH

    更新日期：2019-04-08 00:00:00

  • Scalable salt-templated synthesis of two-dimensional transition metal oxides.

    abstract：:Two-dimensional atomic crystals, such as two-dimensional oxides, have attracted much attention in energy storage because nearly all of the atoms can be exposed to the electrolyte and involved in redox reactions. However, current strategies are largely limited to intrinsically layered compounds. Here we report a genera...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms11296

    authors： Xiao X,Song H,Lin S,Zhou Y,Zhan X,Hu Z,Zhang Q,Sun J,Yang B,Li T,Jiao L,Zhou J,Tang J,Gogotsi Y

    更新日期：2016-04-22 00:00:00

  • Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts.

    abstract：:Parkinson's disease (PD) and Multiple System Atrophy (MSA) are clinically distinctive diseases that feature a common neuropathological hallmark of aggregated α-synuclein. Little is known about how differences in α-synuclein aggregate structure affect disease phenotype. Here, we amplified α-synuclein aggregates from PD...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-13564-w

    authors： Strohäker T,Jung BC,Liou SH,Fernandez CO,Riedel D,Becker S,Halliday GM,Bennati M,Kim WS,Lee SJ,Zweckstetter M

    更新日期：2019-12-04 00:00:00

  • Fast nanoscale addressability of nitrogen-vacancy spins via coupling to a dynamic ferromagnetic vortex.

    abstract：:The core of a ferromagnetic vortex domain creates a strong, localized magnetic field, which can be manipulated on nanosecond timescales, providing a platform for addressing and controlling individual nitrogen-vacancy centre spins in diamond at room temperature, with nanometre-scale resolution. Here, we show that the f...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms11584

    authors： Wolf MS,Badea R,Berezovsky J

    更新日期：2016-06-14 00:00:00

  • Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs.

    abstract：:Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence. However, the impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains unclear. Here we employ quantit...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-07613-z

    authors： Dufourt J,Trullo A,Hunter J,Fernandez C,Lazaro J,Dejean M,Morales L,Nait-Amer S,Schulz KN,Harrison MM,Favard C,Radulescu O,Lagha M

    更新日期：2018-12-05 00:00:00