Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit.

Abstract:

:Cell polarity is the asymmetric compartmentalization of cellular components. An opposing gradient of partitioning-defective protein kinases, atypical protein kinase C (aPKC) and PAR-1, at the cell cortex guides diverse asymmetries in the structure of metazoan cells, but the mechanism underlying their spatial patterning remains poorly understood. Here, we show in Caenorhabditis elegans zygotes that the cortical PAR-1 gradient is patterned as a consequence of dual mechanisms: stabilization of cortical dynamics and protection from aPKC-mediated cortical exclusion. Dual control of cortical PAR-1 depends on a physical interaction with the PRBH-domain protein PAR-2. Using a reconstitution approach in heterologous cells, we demonstrate that PAR-1, PAR-2, and polarized Cdc42-PAR-6-aPKC comprise the minimal network sufficient for the establishment of an opposing cortical gradient. Our findings delineate the mechanism governing cortical polarity, in which a circuit consisting of aPKC and the PRBH-domain protein ensures the local recruitment of PAR-1 to a well-defined cortical compartment.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Ramanujam R,Han Z,Zhang Z,Kanchanawong P,Motegi F

doi

10.1038/s41589-018-0117-1

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

917-927

issue

10

eissn

1552-4450

issn

1552-4469

pii

10.1038/s41589-018-0117-1

journal_volume

14

pub_type

杂志文章
  • Making carbon-nitrogen bonds in biological and chemical synthesis.

    abstract::The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable i...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio0606-284

    authors: Hili R,Yudin AK

    更新日期:2006-06-01 00:00:00

  • Differential roles of human PUS10 in miRNA processing and tRNA pseudouridylation.

    abstract::Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 result...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-019-0420-5

    authors: Song J,Zhuang Y,Zhu C,Meng H,Lu B,Xie B,Peng J,Li M,Yi C

    更新日期:2020-02-01 00:00:00

  • Accessing chemical diversity from the uncultivated symbionts of small marine animals.

    abstract::Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV c...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2537

    authors: Smith TE,Pond CD,Pierce E,Harmer ZP,Kwan J,Zachariah MM,Harper MK,Wyche TP,Matainaho TK,Bugni TS,Barrows LR,Ireland CM,Schmidt EW

    更新日期:2018-02-01 00:00:00

  • Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells.

    abstract::Glycosyltransferases are ubiquitous enzymes that catalyze the assembly of glycoconjugates throughout all kingdoms of nature. A long-standing problem is the rational design of probes that can be used to manipulate glycosyltransferase activity in cells and tissues. Here we describe the rational design and synthesis of a...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.520

    authors: Gloster TM,Zandberg WF,Heinonen JE,Shen DL,Deng L,Vocadlo DJ

    更新日期:2011-03-01 00:00:00

  • Chemical phylogenetics of histone deacetylases.

    abstract::The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.313

    authors: Bradner JE,West N,Grachan ML,Greenberg EF,Haggarty SJ,Warnow T,Mazitschek R

    更新日期:2010-03-01 00:00:00

  • Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria.

    abstract::Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1002

    authors: Adler-Abramovich L,Vaks L,Carny O,Trudler D,Magno A,Caflisch A,Frenkel D,Gazit E

    更新日期:2012-08-01 00:00:00

  • A photochemical snapshot of CD22 binding.

    abstract::Identification of endogenous glycan-binding ligands for cell-surface receptors has been difficult. Incorporation of a photoactive sialic acid analog into B-cell surface glycoproteins suggests that CD22 molecules may cluster by binding carbohydrate antigens on neighboring CD22 molecules. ...

    journal_title:Nature chemical biology

    pub_type: 评论,新闻

    doi:10.1038/nchembio0705-69

    authors: Yarema KJ,Sun Z

    更新日期:2005-07-01 00:00:00

  • HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes.

    abstract::Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-020-0496-y

    authors: Xiao T,Frey G,Fu Q,Lavine CL,Scott DA,Seaman MS,Chou JJ,Chen B

    更新日期:2020-05-01 00:00:00

  • Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases.

    abstract::Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1733

    authors: Larsen JB,Jensen MB,Bhatia VK,Pedersen SL,Bjørnholm T,Iversen L,Uline M,Szleifer I,Jensen KJ,Hatzakis NS,Stamou D

    更新日期:2015-03-01 00:00:00

  • Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesis.

    abstract::Hapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These complex metabolites are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps: a rare Cope rearr...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0003-x

    authors: Newmister SA,Li S,Garcia-Borràs M,Sanders JN,Yang S,Lowell AN,Yu F,Smith JL,Williams RM,Houk KN,Sherman DH

    更新日期:2018-04-01 00:00:00

  • Versatility of biological non-heme Fe(II) centers in oxygen activation reactions.

    abstract::Oxidase and oxygenase enzymes allow the use of relatively unreactive O2 in biochemical reactions. Many of the mechanistic strategies used in nature for this key reaction are represented within the 2-histidine-1-carboxylate facial triad family of non-heme Fe(II)-containing enzymes. The open face of the metal coordinati...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审

    doi:10.1038/nchembio.71

    authors: Kovaleva EG,Lipscomb JD

    更新日期:2008-03-01 00:00:00

  • Discovery of MRSA active antibiotics using primary sequence from the human microbiome.

    abstract::Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonri...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2207

    authors: Chu J,Vila-Farres X,Inoyama D,Ternei M,Cohen LJ,Gordon EA,Reddy BV,Charlop-Powers Z,Zebroski HA,Gallardo-Macias R,Jaskowski M,Satish S,Park S,Perlin DS,Freundlich JS,Brady SF

    更新日期:2016-12-01 00:00:00

  • Decoding Polo-like kinase 1 signaling along the kinetochore-centromere axis.

    abstract::Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet the details of its spatial coordination are obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2060

    authors: Lera RF,Potts GK,Suzuki A,Johnson JM,Salmon ED,Coon JJ,Burkard ME

    更新日期:2016-06-01 00:00:00

  • Interactive exploration of chemical space with Scaffold Hunter.

    abstract::We describe Scaffold Hunter, a highly interactive computer-based tool for navigation in chemical space that fosters intuitive recognition of complex structural relationships associated with bioactivity. The program reads compound structures and bioactivity data, generates compound scaffolds, correlates them in a hiera...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.187

    authors: Wetzel S,Klein K,Renner S,Rauh D,Oprea TI,Mutzel P,Waldmann H

    更新日期:2009-08-01 00:00:00

  • Defining the geometry of the two-component proteasome degron.

    abstract::The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the i...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.521

    authors: Inobe T,Fishbain S,Prakash S,Matouschek A

    更新日期:2011-03-01 00:00:00

  • Nitric oxide activates TRP channels by cysteine S-nitrosylation.

    abstract::Transient receptor potential (TRP) proteins form plasma-membrane cation channels that act as sensors for diverse cellular stimuli. Here, we report a novel activation mechanism mediated by cysteine S-nitrosylation in TRP channels. Recombinant TRPC1, TRPC4, TRPC5, TRPV1, TRPV3 and TRPV4 of the TRPC and TRPV families, wh...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio821

    authors: Yoshida T,Inoue R,Morii T,Takahashi N,Yamamoto S,Hara Y,Tominaga M,Shimizu S,Sato Y,Mori Y

    更新日期:2006-11-01 00:00:00

  • Transcriptional recorder.

    abstract:: ...

    journal_title:Nature chemical biology

    pub_type: 评论,杂志文章

    doi:10.1038/s41589-018-0174-5

    authors: Song Y

    更新日期:2018-12-01 00:00:00

  • miR-CLIP capture of a miRNA targetome uncovers a lincRNA H19-miR-106a interaction.

    abstract::Identifying the interaction partners of noncoding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA crosslinking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-crosslinking and Argonaute 2 i...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1713

    authors: Imig J,Brunschweiger A,Brümmer A,Guennewig B,Mittal N,Kishore S,Tsikrika P,Gerber AP,Zavolan M,Hall J

    更新日期:2015-02-01 00:00:00

  • A conserved water-mediated hydrogen bond network defines bosutinib's kinase selectivity.

    abstract::Kinase inhibitors are important cancer drugs, but they tend to display limited target specificity, and their target profiles are often challenging to rationalize in terms of molecular mechanism. Here we report that the clinical kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of conserved st...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1404

    authors: Levinson NM,Boxer SG

    更新日期:2014-02-01 00:00:00

  • Mechanism of hydrogen activation by [NiFe] hydrogenases.

    abstract::The active site of [NiFe] hydrogenases contains a strictly conserved arginine that suspends a guanidine nitrogen atom <4.5 Å above the nickel and iron atoms. The guanidine headgroup interacts with the side chains of two conserved aspartic acid residues to complete an outer-shell canopy that has thus far proved intract...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1976

    authors: Evans RM,Brooke EJ,Wehlin SA,Nomerotskaia E,Sargent F,Carr SB,Phillips SE,Armstrong FA

    更新日期:2016-01-01 00:00:00

  • Correlating chemical sensitivity and basal gene expression reveals mechanism of action.

    abstract::Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1986

    authors: Rees MG,Seashore-Ludlow B,Cheah JH,Adams DJ,Price EV,Gill S,Javaid S,Coletti ME,Jones VL,Bodycombe NE,Soule CK,Alexander B,Li A,Montgomery P,Kotz JD,Hon CS,Munoz B,Liefeld T,Dančík V,Haber DA,Clish CB,Bittker JA

    更新日期:2016-02-01 00:00:00

  • A bridge between chemistry and biology.

    abstract::Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology. ...

    journal_title:Nature chemical biology

    pub_type:

    doi:10.1038/nchembio0806-392

    authors: Kikuchi K,Kakeya H

    更新日期:2006-08-01 00:00:00

  • Using simple donors to drive the equilibria of glycosyltransferase-catalyzed reactions.

    abstract::We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.638

    authors: Gantt RW,Peltier-Pain P,Cournoyer WJ,Thorson JS

    更新日期:2011-08-21 00:00:00

  • Small-molecule-based regulation of RNA-delivered circuits in mammalian cells.

    abstract::Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0146-9

    authors: Wagner TE,Becraft JR,Bodner K,Teague B,Zhang X,Woo A,Porter E,Alburquerque B,Dobosh B,Andries O,Sanders NN,Beal J,Densmore D,Kitada T,Weiss R

    更新日期:2018-11-01 00:00:00

  • Programmable and printable Bacillus subtilis biofilms as engineered living materials.

    abstract::Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0169-2

    authors: Huang J,Liu S,Zhang C,Wang X,Pu J,Ba F,Xue S,Ye H,Zhao T,Li K,Wang Y,Zhang J,Wang L,Fan C,Lu TK,Zhong C

    更新日期:2019-01-01 00:00:00

  • Prolonged and tunable residence time using reversible covalent kinase inhibitors.

    abstract::Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1817

    authors: Bradshaw JM,McFarland JM,Paavilainen VO,Bisconte A,Tam D,Phan VT,Romanov S,Finkle D,Shu J,Patel V,Ton T,Li X,Loughhead DG,Nunn PA,Karr DE,Gerritsen ME,Funk JO,Owens TD,Verner E,Brameld KA,Hill RJ,Goldstein DM,

    更新日期:2015-07-01 00:00:00

  • ykkC riboswitches employ an add-on helix to adjust specificity for polyanionic ligands.

    abstract::The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0114-4

    authors: Peselis A,Serganov A

    更新日期:2018-09-01 00:00:00

  • Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides.

    abstract::The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our w...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1499

    authors: Mathavan I,Zirah S,Mehmood S,Choudhury HG,Goulard C,Li Y,Robinson CV,Rebuffat S,Beis K

    更新日期:2014-05-01 00:00:00

  • Insights into mucopolysaccharidosis I from the structure and action of α-L-iduronidase.

    abstract::Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding α-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1357

    authors: Bie H,Yin J,He X,Kermode AR,Goddard-Borger ED,Withers SG,James MN

    更新日期:2013-11-01 00:00:00

  • Deciphering the transcriptional regulatory logic of amino acid metabolism.

    abstract::Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and g...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.710

    authors: Cho BK,Federowicz S,Park YS,Zengler K,Palsson BØ

    更新日期:2011-11-13 00:00:00