Molecular stripping in the NF-κB/IκB/DNA genetic regulatory network.

Abstract:

:Genetic switches based on the [Formula: see text] system are master regulators of an array of cellular responses. Recent kinetic experiments have shown that [Formula: see text] can actively remove NF-κB bound to its genetic sites via a process called "molecular stripping." This allows the [Formula: see text] switch to function under kinetic control rather than the thermodynamic control contemplated in the traditional models of gene switches. Using molecular dynamics simulations of coarse-grained predictive energy landscape models for the constituent proteins by themselves and interacting with the DNA we explore the functional motions of the transcription factor [Formula: see text] and its various binary and ternary complexes with DNA and the inhibitor IκB. These studies show that the function of the [Formula: see text] genetic switch is realized via an allosteric mechanism. Molecular stripping occurs through the activation of a domain twist mode by the binding of [Formula: see text] that occurs through conformational selection. Free energy calculations for DNA binding show that the binding of [Formula: see text] not only results in a significant decrease of the affinity of the transcription factor for the DNA but also kinetically speeds DNA release. Projections of the free energy onto various reaction coordinates reveal the structural details of the stripping pathways.

authors

Potoyan DA,Zheng W,Komives EA,Wolynes PG

doi

10.1073/pnas.1520483112

subject

Has Abstract

pub_date

2016-01-05 00:00:00

pages

110-5

issue

1

eissn

0027-8424

issn

1091-6490

pii

1520483112

journal_volume

113

pub_type

杂志文章
  • Development of CD4+ T cells expressing a nominally MHC class I-restricted T cell receptor by two different mechanisms.

    abstract::Differences in T cell receptor (TCR) signaling initiated by interactions among TCRs, coreceptors, and self-peptide-MHC complexes determine the outcome of CD4 versus CD8 lineage of T cell differentiation. The H-2Ld and Kbm3 alloreactive 2C TCR is positively selected by MHC class I Kb and a yet-to-be identified nonclass...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0510561103

    authors: Ge Q,Holler PD,Mahajan VS,Nuygen T,Eisen HN,Chen J

    更新日期:2006-02-07 00:00:00

  • Habitual control of goal selection in humans.

    abstract::Humans choose actions based on both habit and planning. Habitual control is computationally frugal but adapts slowly to novel circumstances, whereas planning is computationally expensive but can adapt swiftly. Current research emphasizes the competition between habits and plans for behavioral control, yet many complex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1506367112

    authors: Cushman F,Morris A

    更新日期:2015-11-10 00:00:00

  • Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP.

    abstract::After the start of transcription, the 5' ends of eukaryotic mRNA molecules are modified by the addition of a guanylyl residue to form a cap structure, G(5')ppp(5')N. The guanylyltransferase (GTP:mRNA guanylyltransferase, EC 2.7.7.50) reaction responsible for cap formation usually proceeds via a covalent enzyme-GMP int...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.2.507

    authors: Ahola T,Kääriäinen L

    更新日期:1995-01-17 00:00:00

  • Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function.

    abstract::Neurog3 (Neurogenin 3 or Ngn3) is both necessary and sufficient to induce endocrine islet cell differentiation from embryonic pancreatic progenitors. Since robust Neurog3 expression has not been detected in hormone-expressing cells, Neurog3 is used as an endocrine progenitor marker and regarded as dispensable for the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0904247106

    authors: Wang S,Jensen JN,Seymour PA,Hsu W,Dor Y,Sander M,Magnuson MA,Serup P,Gu G

    更新日期:2009-06-16 00:00:00

  • Comparative mapping of Andropogoneae: Saccharum L. (sugarcane) and its relation to sorghum and maize.

    abstract::Comparative genetic maps of Papuan Saccharum officinarum L. (2n = 80) and S. robustum (2n = 80) were constructed by using single-dose DNA markers (SDMs). SDM-framework maps of S. officinarum and S. robustum were compared with genetic maps of sorghum and maize by way of anchor restriction fragment length polymorphism p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.26.14261

    authors: Guimarães CT,Sills GR,Sobral BW

    更新日期:1997-12-23 00:00:00

  • Primary photochemical event in vision: proton translocation.

    abstract::Picosecond studies of rhodopsin in low-temperature glasses have been carried out in order to observe directly the risetime of prelumirhodopsin, the first intermediate in the visual pathway. Only at 20 K or below can the risetime of this intermediate be resolved and even at 4 K it is astoundingly rapid, about 36 psec. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.8.3119

    authors: Peters K,Applebury ML,Rentzepis PM

    更新日期:1977-08-01 00:00:00

  • Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation.

    abstract::The midcycle luteinizing hormone (LH) surge triggers several tightly linked ovarian processes, including steroidogenesis, oocyte maturation, and ovulation. We designed studies to determine whether epidermal growth factor receptor (EGFR)-mediated signaling might serve as a common regulator of these activities. Our resu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0508521102

    authors: Jamnongjit M,Gill A,Hammes SR

    更新日期:2005-11-08 00:00:00

  • Plasma membrane/cell wall perturbation activates a novel cell cycle checkpoint during G1 in Saccharomyces cerevisiae.

    abstract::Cellular wound healing or the repair of plasma membrane/cell wall damage (plasma membrane damage) occurs frequently in nature. Although various cellular perturbations, such as DNA damage, spindle misalignment, and impaired daughter cell formation, are monitored by cell cycle checkpoint mechanisms in budding yeast, whe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1523824113

    authors: Kono K,Al-Zain A,Schroeder L,Nakanishi M,Ikui AE

    更新日期:2016-06-21 00:00:00

  • Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity.

    abstract::Intramembrane proteolysis is a new paradigm in biology that controls signaling events throughout evolution. Hydrolysis of peptide bonds is thought to occur within the normally hydrophobic membrane environment, but insights into this unusual activity have been lacking because of difficulty in recapitulating activity in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0408306102

    authors: Urban S,Wolfe MS

    更新日期:2005-02-08 00:00:00

  • Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication.

    abstract::Animal models of human cytomegalovirus (CMV) infections have not been available to study pathogenesis or to evaluate antiviral drugs. Severe combined immunodeficient mice implanted with human fetal tissues (SCID-hu) were found to support CMV replication and may provide a model for this species-specific virus. When con...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.1.104

    authors: Mocarski ES,Bonyhadi M,Salimi S,McCune JM,Kaneshima H

    更新日期:1993-01-01 00:00:00

  • Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains.

    abstract::Endoplasmic reticulum (ER) stress sensors use a related luminal domain to monitor the unfolded protein load and convey the signal to downstream effectors, signaling an unfolded protein response (UPR) that maintains compartment-specific protein folding homeostasis. Surprisingly, perturbation of cellular lipid compositi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1217611110

    authors: Volmer R,van der Ploeg K,Ron D

    更新日期:2013-03-19 00:00:00

  • Overproduction of the epsilon subunit of DNA polymerase III counteracts the SOS mutagenic response of Escherichia coli.

    abstract::It has been found that the mutator phenotype of the recA441 and recA730 strains that express the SOS response constitutively is suppressed by pIP1, a high-copy plasmid carrying the dnaQ gene encoding the 3'----5' exonuclease subunit (epsilon) of DNA polymerase III. We have constructed plasmid pIP11, in which the dnaQ ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.23.9124

    authors: Jonczyk P,Fijalkowska I,Ciesla Z

    更新日期:1988-12-01 00:00:00

  • Local alterations of Krox-20 and Hox gene expression in the hindbrain suggest lack of rhombomeres 4 and 5 in homozygote null Hoxa-1 (Hox-1.6) mutant embryos.

    abstract::It is unknown whether cross-regulatory interactions between homeotic genes, which have been shown to play an important role in the maintenance of their expression domains during Drosophila development, are also important during mammalian development. We have analyzed here the expression of Hox genes in Hoxa-1 (Hox-1.6...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.16.7666

    authors: Dollé P,Lufkin T,Krumlauf R,Mark M,Duboule D,Chambon P

    更新日期:1993-08-15 00:00:00

  • Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties.

    abstract::Phase separation of multivalent protein and RNA molecules underlies the biogenesis of biomolecular condensates such as membraneless organelles. In vivo, these condensates encompass hundreds of distinct types of molecules that typically organize into multilayered structures supporting the differential partitioning of m...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1821038116

    authors: Boeynaems S,Holehouse AS,Weinhardt V,Kovacs D,Van Lindt J,Larabell C,Van Den Bosch L,Das R,Tompa PS,Pappu RV,Gitler AD

    更新日期:2019-04-16 00:00:00

  • Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants.

    abstract::Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.17.8225

    authors: Carlson J,Sakamoto Y,Laurell CB,Madison J,Watkins S,Putnam FW

    更新日期:1992-09-01 00:00:00

  • Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate.

    abstract::Heat-shock protein of 90 kDa (Hsp90) is an essential molecular chaperone that adopts different 3D structures associated with distinct nucleotide states: a wide-open, V-shaped dimer in the apo state and a twisted, N-terminally closed dimer with ATP. Although the N domain is known to mediate ATP binding, how Hsp90 sense...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1516167113

    authors: Sung N,Lee J,Kim JH,Chang C,Joachimiak A,Lee S,Tsai FT

    更新日期:2016-03-15 00:00:00

  • Successful rescue of microsurgically produced homozygous uniparental mouse embryos via production of aggregation chimeras.

    abstract::Homozygous uniparental mouse embryos, produced by microsurgical removal of the male pronucleus from fertilized eggs and diploidization of the female pronucleus with cytochalasin, were surrounded with blastomeres from normal embryos to produce chimeric embryos. A few of these chimeras developed into viable adults, and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.17.6509

    authors: Anderegg C,Markert CL

    更新日期:1986-09-01 00:00:00

  • Components of fitness become effectively neutral in equilibrium populations.

    abstract::If, because of trade-offs or similar considerations, components of fitness are negatively correlated in equilibrium populations, they may then exhibit no correlation with total fitness. Lack of correlation with fitness is a fundamental characteristic of selective neutrality. Hence, selectively important traits become ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.5.2018

    authors: Reeve R,Smith E,Wallace B

    更新日期:1990-03-01 00:00:00

  • CDK5 activator protein p25 preferentially binds and activates GSK3β.

    abstract::Glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5) are tau kinases and have been proposed to contribute to the pathogenesis of Alzheimer's disease. The 3D structures of these kinases are remarkably similar, which led us to hypothesize that both might be capable of binding cyclin proteins--the act...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1402627111

    authors: Chow HM,Guo D,Zhou JC,Zhang GY,Li HF,Herrup K,Zhang J

    更新日期:2014-11-11 00:00:00

  • Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum.

    abstract::Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtai...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.2.705

    authors: Bianchi DW,Zickwolf GK,Weil GJ,Sylvester S,DeMaria MA

    更新日期:1996-01-23 00:00:00

  • Mitochondrial transfer between cells can rescue aerobic respiration.

    abstract::Current theory indicates that mitochondria were obtained 1.5 billion years ago from an ancient prokaryote. The mitochondria provided the capacity for aerobic respiration, the creation of the eukaryotic cell, and eventually complex multicellular organisms. Recent reports have found that mitochondria play essential role...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0510511103

    authors: Spees JL,Olson SD,Whitney MJ,Prockop DJ

    更新日期:2006-01-31 00:00:00

  • Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

    abstract::Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.8.2926

    authors: Hantaï D,Rao JS,Festoff BW

    更新日期:1990-04-01 00:00:00

  • Simplified method in polynucleotide helix-coil transition theory including binding of complementary monomer.

    abstract::The grand partition function for a long linear system of alternating alpha and beta sequences with the restraint of a fixed number, N(alphabeta), of alphabeta boundaries depends in an extremely simple way on the alpha-sequence and beta-sequence grand partition functions, xi(alpha) and xi(beta). When the restraint is r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.5.1165

    authors: Hill TL

    更新日期:1972-05-01 00:00:00

  • A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity.

    abstract::Several domains of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein have been identified that are involved in HIV-1-mediated membrane fusion. One domain that is involved in membrane fusion is the hydrophobic amino terminus of the HIV-1 transmembrane glycoprotein gp41. Here we show that a polar sub...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.1.70

    authors: Freed EO,Delwart EL,Buchschacher GL Jr,Panganiban AT

    更新日期:1992-01-01 00:00:00

  • Interactions among Hageman factor, plasma prekallikrein, high molecular weight kininogen, and plasma thromboplastin antecedent.

    abstract::To investigate the earliest steps of the intrinsic clotting pathway, Hageman factor (Factor XII) was exposed to Sephadex gels to which ellagic acid had been adsorbed; Hageman factor was then separated from the gels and studied in the fluid phase. Sephadex-ellagic acid-exposed Hageman factor, whether purified or in pla...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.2.958

    authors: Ratnoff OD,Saito H

    更新日期:1979-02-01 00:00:00

  • Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling.

    abstract::Toll-like receptor signaling and subsequent activation of NF-κB- and MAPK-dependent genes during infection play an important role in antimicrobial host defense. The YopJ protein of pathogenic Yersinia species inhibits NF-κB and MAPK signaling, resulting in blockade of NF-κB-dependent cytokine production and target cel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1403252111

    authors: Philip NH,Dillon CP,Snyder AG,Fitzgerald P,Wynosky-Dolfi MA,Zwack EE,Hu B,Fitzgerald L,Mauldin EA,Copenhaver AM,Shin S,Wei L,Parker M,Zhang J,Oberst A,Green DR,Brodsky IE

    更新日期:2014-05-20 00:00:00

  • Complexity transmission during replication.

    abstract::The transmission of complexity during DNA replication has been investigated to clarify the significance of this molecular property in a deterministic process. Complexity was equated with the amount of randomness within an ordered molecular structure and measured by the entropy of a posteriori probabilities for discret...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.5.2288

    authors: Davis BK

    更新日期:1979-05-01 00:00:00

  • Antibodies specific to the retinoic acid human nuclear receptors alpha and beta.

    abstract::Two cDNAs encoding two human receptors for retinoic acid (RA), RAR-alpha and RAR-beta, have been characterized recently. Synthetic peptides corresponding to the cDNA-deduced amino acid sequences unique to RAR-alpha and RAR-beta were used to generate anti-RAR-alpha antiserum (SP171) and anti-RAR-beta antisera (SP172 an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.9.3089

    authors: Gaub MP,Lutz Y,Ruberte E,Petkovich M,Brand N,Chambon P

    更新日期:1989-05-01 00:00:00

  • Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line.

    abstract::Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, α-ketoacids, and α-hydroxyacids originating from amino acid metabolism as well as polyketide-deri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1204232109

    authors: Peng C,Pu JY,Song LQ,Jian XH,Tang MC,Tang GL

    更新日期:2012-05-29 00:00:00

  • Resurgence of responding after the cessation of response-independent reinforcement.

    abstract::In an autoshaping experiment, food-deprived pigeons pecked rapidly at a moving dot that preceded the delivery of food. When the moving dot and food were no longer correlated, the rate of pecking dropped nearly to zero. When, subsequently, no food was given, pecking reappeared at a high rate (nearly 200 pecks per min f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.10.6251

    authors: Epstein R,Skinner BF

    更新日期:1980-10-01 00:00:00