The bacterial curli system possesses a potent and selective inhibitor of amyloid formation.

Abstract:

:Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations and maintained CsgA in a non-β-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human α-synuclein, but not Aβ42, in vitro. We identified a common D-Q-Φ-X0,1-G-K-N-ζ-E motif in CsgC client proteins that is not found in Aβ42. CsgC is therefore both an efficient and selective amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature that distinguishes functional amyloids from disease-associated amyloids.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Evans ML,Chorell E,Taylor JD,Åden J,Götheson A,Li F,Koch M,Sefer L,Matthews SJ,Wittung-Stafshede P,Almqvist F,Chapman MR

doi

10.1016/j.molcel.2014.12.025

subject

Has Abstract

pub_date

2015-02-05 00:00:00

pages

445-55

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(14)01003-X

journal_volume

57

pub_type

杂志文章
  • AMPK phosphorylation of raptor mediates a metabolic checkpoint.

    abstract::AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.03.003

    authors: Gwinn DM,Shackelford DB,Egan DF,Mihaylova MM,Mery A,Vasquez DS,Turk BE,Shaw RJ

    更新日期:2008-04-25 00:00:00

  • Activation of RNA polymerase I transcription by cockayne syndrome group B protein and histone methyltransferase G9a.

    abstract::Cockayne syndrome group B (CSB) protein plays a role in both transcription-coupled DNA repair and transcriptional regulation of all three classes of nuclear RNA polymerases. Here we show that a complex consisting of CSB, RNA polymerase I (Pol I), and histone methyltransferase G9a is present at active rRNA genes. G9a m...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.06.021

    authors: Yuan X,Feng W,Imhof A,Grummt I,Zhou Y

    更新日期:2007-08-17 00:00:00

  • Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells.

    abstract::The Ca2+ -activated K+ channel KCa3.1 is required for Ca2+ influx and the subsequent activation of B and T cells. Inhibitors of KCa3.1 are in development to treat autoimmune diseases and transplant rejection, underscoring the importance in understanding how these channels are regulated. We show that nucleoside diphosp...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.11.012

    authors: Srivastava S,Li Z,Ko K,Choudhury P,Albaqumi M,Johnson AK,Yan Y,Backer JM,Unutmaz D,Coetzee WA,Skolnik EY

    更新日期:2006-12-08 00:00:00

  • Gene-Specific Control of tRNA Expression by RNA Polymerase II.

    abstract::Increasing evidence suggests that tRNA levels are dynamically and specifically regulated in response to internal and external cues to modulate the cellular translational program. However, the molecular players and the mechanisms regulating the gene-specific expression of tRNAs are still unknown. Using an inducible aux...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.03.023

    authors: Gerber A,Ito K,Chu CS,Roeder RG

    更新日期:2020-05-21 00:00:00

  • Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer.

    abstract::Distinctive from their normal counterparts, cancer cells exhibit unique metabolic dependencies on glutamine to fuel anabolic processes. Specifically, pancreatic ductal adenocarcinoma (PDAC) cells rely on an unconventional metabolic pathway catalyzed by aspartate aminotransferase, malate dehydrogenase 1 (MDH1), and mal...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.09.028

    authors: Wang YP,Zhou W,Wang J,Huang X,Zuo Y,Wang TS,Gao X,Xu YY,Zou SW,Liu YB,Cheng JK,Lei QY

    更新日期:2016-11-17 00:00:00

  • The nucle(ol)ar Tif6p and Efl1p are required for a late cytoplasmic step of ribosome synthesis.

    abstract::Deletion of elongation factor-like 1 (Efl1p), a cytoplasmic GTPase homologous to the ribosomal translocases EF-G/EF-2, results in nucle(ol)ar pre-rRNA processing and pre-60S subunits export defects. Efl1p interacts genetically with Tif6p, a nucle(ol)ar protein stably associated with pre-60S subunits and required for t...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00403-8

    authors: Senger B,Lafontaine DL,Graindorge JS,Gadal O,Camasses A,Sanni A,Garnier JM,Breitenbach M,Hurt E,Fasiolo F

    更新日期:2001-12-01 00:00:00

  • ASF1a Promotes Non-homologous End Joining Repair by Facilitating Phosphorylation of MDC1 by ATM at Double-Strand Breaks.

    abstract::Double-strand breaks (DSBs) of DNA in eukaryotic cells are predominantly repaired by non-homologous end joining (NHEJ). The histone chaperone anti-silencing factor 1a (ASF1a) interacts with MDC1 and is recruited to sites of DSBs to facilitate the interaction of phospho-ATM with MDC1 and phosphorylation of MDC1, which ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.08.021

    authors: Lee KY,Im JS,Shibata E,Dutta A

    更新日期:2017-10-05 00:00:00

  • A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity.

    abstract::FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00353-7

    authors: Rocchi S,Picard F,Vamecq J,Gelman L,Potier N,Zeyer D,Dubuquoy L,Bac P,Champy MF,Plunket KD,Leesnitzer LM,Blanchard SG,Desreumaux P,Moras D,Renaud JP,Auwerx J

    更新日期:2001-10-01 00:00:00

  • Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest.

    abstract::Autophagy, a catabolic pathway that delivers cellular components to lysosomes for degradation, can be activated by stressful conditions such as nutrient starvation and endoplasmic reticulum (ER) stress. We report that thapsigargin, an ER stressor widely used to induce autophagy, in fact blocks autophagy. Thapsigargin ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.04.024

    authors: Ganley IG,Wong PM,Gammoh N,Jiang X

    更新日期:2011-06-24 00:00:00

  • Histone Acetyltransferase 1 Links Metabolism and Transcription to Cell-Cycle Progression.

    abstract::HAT1 is an essential gene in mammals that acetylates newly synthesized histone H4 and is involved in chromatin assembly and genome maintenance. In this issue of Molecular Cell, Gruber et al. (2019) show that HAT1 binds to and stimulates H4 gene expression in a growth-factor- and glucose-dependent manner. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2019.08.004

    authors: Denu JM

    更新日期:2019-08-22 00:00:00

  • A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif.

    abstract::HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80056-8

    authors: Margottin F,Bour SP,Durand H,Selig L,Benichou S,Richard V,Thomas D,Strebel K,Benarous R

    更新日期:1998-03-01 00:00:00

  • Insights into a Mysterious CRISPR Adaptation Factor, Cas4.

    abstract::Cas4 nucleases are conserved factors in many CRISPR systems, yet their molecular role has remained enigmatic. In this issue of Molecular Cell, Shiimori et al. (2018) report that two Cas4 nucleases together determine the size, orientation, and PAM for foreign DNA snippets acquired by CRISPR loci as immunological memory...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.05.028

    authors: Hou Z,Zhang Y

    更新日期:2018-06-07 00:00:00

  • Gene repression by coactivator repulsion.

    abstract::We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some of the endogenous IFN-beta enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(05)00081-x

    authors: Senger K,Merika M,Agalioti T,Yie J,Escalante CR,Chen G,Aggarwal AK,Thanos D

    更新日期:2000-10-01 00:00:00

  • A role for SIRT1 in the hypoxic response.

    abstract::In this issue of Molecular Cell, Lim et al. (2010) show that SIRT1 deacetylates HIF-1alpha and regulates its ability to respond to hypoxia, revealing yet another important function of SIRT1 and suggesting a connection between HIF function in aging and sirtuin enzymes. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2010.06.015

    authors: Leiser SF,Kaeberlein M

    更新日期:2010-06-25 00:00:00

  • Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism.

    abstract::Circadian rhythms in mammals are generated by a transcriptional negative feedback loop that is driven primarily by oscillations of PER and CRY, which inhibit their own transcriptional activators, CLOCK and BMAL1. Current models posit that CRY is the dominant repressor, while PER may play an accessory role. In this stu...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.10.012

    authors: Chen R,Schirmer A,Lee Y,Lee H,Kumar V,Yoo SH,Takahashi JS,Lee C

    更新日期:2009-11-13 00:00:00

  • The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells.

    abstract::Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.11.001

    authors: Seisenberger S,Andrews S,Krueger F,Arand J,Walter J,Santos F,Popp C,Thienpont B,Dean W,Reik W

    更新日期:2012-12-28 00:00:00

  • ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression.

    abstract::Metazoan transcription factors typically regulate large numbers of genes. Here we identify via a CRISPR-Cas9 genetic screen ZNF410, a pentadactyl DNA-binding protein that in human erythroid cells directly activates only a single gene, the NuRD component CHD4. Specificity is conveyed by two highly evolutionarily conser...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.11.006

    authors: Lan X,Ren R,Feng R,Ly LC,Lan Y,Zhang Z,Aboreden N,Qin K,Horton JR,Grevet JD,Mayuranathan T,Abdulmalik O,Keller CA,Giardine B,Hardison RC,Crossley M,Weiss MJ,Cheng X,Shi J,Blobel GA

    更新日期:2021-01-21 00:00:00

  • Advances in CLIP Technologies for Studies of Protein-RNA Interactions.

    abstract::RNA binding proteins (RBPs) regulate all aspects in the life cycle of RNA molecules. To elucidate the elements that guide RNA specificity, regulatory mechanisms, and functions of RBPs, methods that identify direct endogenous protein-RNA interactions are particularly valuable. UV crosslinking and immunoprecipitation (C...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2018.01.005

    authors: Lee FCY,Ule J

    更新日期:2018-02-01 00:00:00

  • Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β1-Adrenergic Receptor.

    abstract::Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β1-adrenergic receptor (β1-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by β1-ARs, leading to in...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.08.001

    authors: Su M,Zhu L,Zhang Y,Paknejad N,Dey R,Huang J,Lee MY,Williams D,Jordan KD,Eng ET,Ernst OP,Meyerson JR,Hite RK,Walz T,Liu W,Huang XY

    更新日期:2020-10-01 00:00:00

  • The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5.

    abstract::Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here,...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.09.018

    authors: Sekine Y,Hatanaka R,Watanabe T,Sono N,Iemura S,Natsume T,Kuranaga E,Miura M,Takeda K,Ichijo H

    更新日期:2012-12-14 00:00:00

  • Spatial Organization of Single mRNPs at Different Stages of the Gene Expression Pathway.

    abstract::mRNAs form ribonucleoprotein complexes (mRNPs) by association with proteins that are crucial for mRNA metabolism. While the mRNP proteome has been well characterized, little is known about mRNP organization. Using a single-molecule approach, we show that mRNA conformation changes depending on its cellular localization...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.10.010

    authors: Adivarahan S,Livingston N,Nicholson B,Rahman S,Wu B,Rissland OS,Zenklusen D

    更新日期:2018-11-15 00:00:00

  • Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.

    abstract::Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics in mammalian cells. Here, we illustrate the utility of this appr...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.01.014

    authors: Wong JV,Yao G,Nevins JR,You L

    更新日期:2011-02-04 00:00:00

  • Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.

    abstract::Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.01.013

    authors: Ma S,Shen Q,Zhao LH,Mao C,Zhou XE,Shen DD,de Waal PW,Bi P,Li C,Jiang Y,Wang MW,Sexton PM,Wootten D,Melcher K,Zhang Y,Xu HE

    更新日期:2020-02-06 00:00:00

  • RNA Structure Switches RBP Binding.

    abstract::RNA sequence motifs are not sufficient for association with RBPs. In this issue of Molecular Cell, Taliaferro et al. (2016) demonstrate that, other than sequence motif, RNA secondary structure plays a repressive role on RBP binding, both in vitro and in vivo. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2016.10.006

    authors: Luo Z,Yang Q,Yang L

    更新日期:2016-10-20 00:00:00

  • Pif1-Family Helicases Support Fork Convergence during DNA Replication Termination in Eukaryotes.

    abstract::The convergence of two DNA replication forks creates unique problems during DNA replication termination. In E. coli and SV40, the release of torsional strain by type II topoisomerases is critical for converging replisomes to complete DNA synthesis, but the pathways that mediate fork convergence in eukaryotes are unkno...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2019.01.040

    authors: Deegan TD,Baxter J,Ortiz Bazán MÁ,Yeeles JTP,Labib KPM

    更新日期:2019-04-18 00:00:00

  • Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence.

    abstract::S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenet...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2020.03.004

    authors: Haws SA,Yu D,Ye C,Wille CK,Nguyen LC,Krautkramer KA,Tomasiewicz JL,Yang SE,Miller BR,Liu WH,Igarashi K,Sridharan R,Tu BP,Cryns VL,Lamming DW,Denu JM

    更新日期:2020-04-16 00:00:00

  • Control of actin turnover by a salmonella invasion protein.

    abstract::Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(04)00053-x

    authors: McGhie EJ,Hayward RD,Koronakis V

    更新日期:2004-02-27 00:00:00

  • Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis.

    abstract::The role of the protein kinase Akt in cell migration is incompletely understood. Here we show that sphingosine-1-phosphate (S1P)-induced endothelial cell migration requires the Akt-mediated phosphorylation of the G protein-coupled receptor (GPCR) EDG-1. Activated Akt binds to EDG-1 and phosphorylates the third intrace...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00324-0

    authors: Lee MJ,Thangada S,Paik JH,Sapkota GP,Ancellin N,Chae SS,Wu M,Morales-Ruiz M,Sessa WC,Alessi DR,Hla T

    更新日期:2001-09-01 00:00:00

  • SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress.

    abstract::When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activi...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.04.027

    authors: Szoradi T,Schaeff K,Garcia-Rivera EM,Itzhak DN,Schmidt RM,Bircham PW,Leiss K,Diaz-Miyar J,Chen VK,Muzzey D,Borner GHH,Schuck S

    更新日期:2018-06-21 00:00:00

  • Stress-induced map kinase Hog1 is part of transcription activation complexes.

    abstract::In response to hyperosmotic environments, most eukaryotic cells activate a specialized mitogen-activated protein (MAP) kinase pathway. In S. cerevisiae, the key protein kinase, Hog1, coordinates the transcriptional induction of a variety of genes devoted to osmoadaptation and general stress protection. Depending on th...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00221-0

    authors: Alepuz PM,Jovanovic A,Reiser V,Ammerer G

    更新日期:2001-04-01 00:00:00