Abstract:
:Integration of chemical probes into proteomic workflows enables the interrogation of protein activity, rather than abundance. Current methods limit the biological contexts that can be addressed due to sample homogenization, signal-averaging, and bias toward abundant proteins. Here we report a platform that integrates family-wide chemical probes with proximity-dependent oligonucleotide amplification and imaging to quantify enzyme activity in native contexts with high spatial resolution. Application of this method, activity-dependent proximity ligation (ADPL), to serine hydrolase and cysteine protease enzymes enables quantification of differential enzyme activity resulting from endogenous changes in localization and expression. In a competitive format, small-molecule target engagement with endogenous proteins in live cells can be quantified. Finally, retention of sample architecture enables interrogation of complex environments such as cellular co-culture and patient samples. ADPL should be amenable to diverse probe and protein families to detect active enzymes at scale and resolution out of reach with current methods.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Li G,Montgomery JE,Eckert MA,Chang JW,Tienda SM,Lengyel E,Moellering REdoi
10.1038/s41467-017-01854-0subject
Has Abstractpub_date
2017-11-24 00:00:00pages
1775issue
1issn
2041-1723pii
10.1038/s41467-017-01854-0journal_volume
8pub_type
杂志文章abstract::Artificial photosynthesis is a vibrant field of research aiming at converting abundant, low energy molecules such as water, nitrogen or carbon dioxide into fuels or useful chemicals by means of solar energy input. Photo-electrochemical reduction of carbon dioxide is an appealing strategy, aiming at reducing the greenh...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17125-4
更新日期:2020-07-13 00:00:00
abstract::The Cdc45-MCM-GINS (CMG) helicase unwinds DNA during the elongation step of eukaryotic genome duplication and this process depends on the MCM ATPase function. Whether CMG translocation occurs on single- or double-stranded DNA and how ATP hydrolysis drives DNA unwinding remain open questions. Here we use cryo-electron ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10708
更新日期:2016-02-18 00:00:00
abstract::Nanocarrier administration has primarily been restricted to intermittent bolus injections with limited available options for sustained delivery in vivo. Here, we demonstrate that cylinder-to-sphere transitions of self-assembled filomicelle (FM) scaffolds can be employed for sustained delivery of monodisperse micellar ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03001-9
更新日期:2018-02-12 00:00:00
abstract::Oxygen defect control has long been considered an important route to functionalizing complex oxide films. However, the nature of oxygen defects in thin films is often not investigated beyond basic redox chemistry. One of the model examples for oxygen-defect studies is the layered Ruddlesden-Popper phase La2-xSr x CuO4...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02568-z
更新日期:2018-01-08 00:00:00
abstract::Metastasis-associated recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC), however, the underlying mechanisms remain largely elusive. In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, associated with poor survival, early recurrence and more satelli...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10364-0
更新日期:2019-06-07 00:00:00
abstract::Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple ch...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15455-x
更新日期:2020-04-07 00:00:00
abstract::The original version of this Article was missing the ORCID ID of Professor Nicola Pugno.Also in the original version of this Article, the third to last sentence of the fourth paragraph of the Results incorrectly read 'However, the stepwise addition of CNTs increases the self-entanglement and thereby the compressive st...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-017-02372-9
更新日期:2018-01-09 00:00:00
abstract::Detection of microbial components such as lipopolysaccharide (LPS) by Toll-like receptor 4 (TLR4) on macrophages induces a robust pro-inflammatory response that is dependent on metabolic reprogramming. These innate metabolic changes have been compared to aerobic glycolysis in tumour cells. However, the mechanisms by w...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17669-5
更新日期:2020-07-30 00:00:00
abstract::Post-translational protein modifications are systems designed to expand restricted genomic information through functional conversion of target molecules. Ubiquitin-like post-translational modifiers regulate numerous cellular events through their covalent linkages to target protein(s) by an enzymatic cascade analogous ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1182
更新日期:2011-02-08 00:00:00
abstract::Structural DNA nanotechnology seeks to build synthetic molecular machinery from DNA. DNA nanomachines are artificially designed assemblies that switch between defined conformations in response to an external cue. Though it has proved possible to create DNA machines and rudimentary walkers, the function of such autonom...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1340
更新日期:2011-06-07 00:00:00
abstract::The burial of terrestrial organic carbon (terrOC) in marine sediments contributes to the regulation of atmospheric CO2 on geological timescales and may mitigate positive feedback to present-day climate warming. However, the fate of terrOC in marine settings is debated, with uncertainties regarding its degradation duri...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03192-1
更新日期:2018-02-23 00:00:00
abstract::Cascade reactions initiated by radical addition to alkynes are synthetically very attractive because they enable access to highly complex molecular skeletons in only few synthetic steps under usually mild conditions. Here we report a general radical cascade reaction of alkynes, N-fluoroarylsulfonimides and alcohols, e...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8011
更新日期:2015-04-22 00:00:00
abstract::Eukaryotic cyclic nucleotide-modulated (CNM) ion channels perform various physiological roles by opening in response to cyclic nucleotides binding to a specialized cyclic nucleotide-binding domain. Despite progress in structure-function analysis, the conformational rearrangements underlying the gating of these channel...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12789
更新日期:2016-09-20 00:00:00
abstract::Complex oxide heterointerfaces and van der Waals heterostructures present two versatile but intrinsically different platforms for exploring emergent quantum phenomena and designing new functionalities. The rich opportunity offered by the synergy between these two classes of materials, however, is yet to be charted. He...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15191-2
更新日期:2020-03-17 00:00:00
abstract::Cold- and β3-adrenoceptor agonist-induced sympathetic activation leads to angiogenesis and UCP1-dependent thermogenesis in mouse brown and white adipose tissues. Here we show that endothelial production of PDGF-CC during white adipose tissue (WAT) angiogenesis regulates WAT browning. We find that genetic deletion of e...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12152
更新日期:2016-08-05 00:00:00
abstract::Identification of the complete set of translated genes of viruses is important to understand viral replication and pathogenesis as well as for therapeutic approaches to control viral infection. Here, we use chemical proteomics, integrating bio-orthogonal non-canonical amino acid tagging and high-resolution mass spectr...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18718-9
更新日期:2020-09-29 00:00:00
abstract::Silk and silk fibroin, the biomaterial from nature, nowadays are being widely utilized in many cutting-edge micro/nanodevices/systems via advanced micro/nanofabrication techniques. Herein, for the first time to our knowledge, we report aqueous multiphoton lithography of diversiform-regenerated-silk-fibroin-centric ink...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9612
更新日期:2015-10-16 00:00:00
abstract::In response to virus infection, RIG-I-like receptors (RLRs) sense virus RNA and induce MAVS to form prion-like aggregates to further propagate antiviral signalling. Although monomeric MAVS recombinant protein can assemble into prion-like filaments spontaneously in vitro, endogenous MAVS in cells is prevented from aggr...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15676
更新日期:2017-06-13 00:00:00
abstract::Pentatricopeptide repeat (PPR) proteins control diverse aspects of RNA metabolism in eukaryotic cells. Although recent computational and structural studies have provided insights into RNA recognition by PPR proteins, their highly insoluble nature and inconsistencies between predicted and observed modes of RNA binding ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6729
更新日期:2014-12-17 00:00:00
abstract::Droplet interactions with compliant materials are familiar, but surprisingly complex processes of importance to the manufacturing, chemical, and garment industries. Despite progress-previous research indicates that mesoscopic substrate deformations can enhance droplet drying or slow down spreading dynamics-our underst...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12093-w
更新日期:2019-10-21 00:00:00
abstract::Roughly 40% of the Earth's total heat flow is powered by radioactive decays in the crust and mantle. Geo-neutrinos produced by these decays provide important clues about the origin, formation and thermal evolution of our planet, as well as the composition of its interior. Previous measurements of geo-neutrinos have al...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15989
更新日期:2017-07-10 00:00:00
abstract::The high photon flux and femtosecond pulse duration of hard X-ray free-electron lasers have spurred a large variety of novel and fascinating experiments in physical, chemical and biological sciences. Many of these experiments depend fundamentally on a clean, well-defined wavefront. Here we explore the wavefront proper...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1950
更新日期:2012-07-10 00:00:00
abstract::Glacier retreat is a worldwide phenomenon with important consequences for the hydrological cycle and downstream ecosystem structure and functioning. To determine the effects of glacier retreat on aquatic communities, we conducted a 4-year flow manipulation in a tropical glacier-fed stream. Compared with an adjacent re...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12025
更新日期:2016-06-24 00:00:00
abstract::Despite extensive studies on transcription mechanisms, it is unknown how termination complexes are disassembled, especially in what order the essential components dissociate. Our single-molecule fluorescence study unveils that RNA transcript release precedes RNA polymerase (RNAP) dissociation from the DNA template muc...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-14200-3
更新日期:2020-01-23 00:00:00
abstract::In all of the diverse areas of science where waves play an important role, one of the most fundamental solutions of the corresponding wave equation is a stationary wave with constant intensity. The most familiar example is that of a plane wave propagating in free space. In the presence of any Hermitian potential, a wa...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8257
更新日期:2015-07-08 00:00:00
abstract::The engineering of nanoscale features enables the properties of solid-state materials to be tuned. Here, we show the tunable preparation of cuprous sulfide nanocrystals ranging in internal structures from single-domain to multi-domain. The synthetic method utilizes in-situ oxidation to grow nanocrystals with a control...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11229-2
更新日期:2019-07-23 00:00:00
abstract::Activation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activat...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07338-z
更新日期:2018-11-23 00:00:00
abstract::Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene c...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16718-3
更新日期:2020-06-11 00:00:00
abstract::Coherence in light-matter interaction is a necessary ingredient if light is used to control the quantum state of a material system. Coherent effects are firmly associated with isolated systems kept at low temperature. The exceedingly fast dephasing in condensed matter environments, in particular at elevated temperatur...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3953
更新日期:2013-01-01 00:00:00
abstract::Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins level...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11934
更新日期:2016-06-21 00:00:00