Net charge per residue modulates conformational ensembles of intrinsically disordered proteins.

Abstract:

:Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups--a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs.

authors

Mao AH,Crick SL,Vitalis A,Chicoine CL,Pappu RV

doi

10.1073/pnas.0911107107

subject

Has Abstract

pub_date

2010-05-04 00:00:00

pages

8183-8

issue

18

eissn

0027-8424

issn

1091-6490

pii

0911107107

journal_volume

107

pub_type

杂志文章
  • A neurohypophyseal hormone analog with selective oxytocin-like activities and resistance to enzymatic inactivation: an approach to the design of peptide drugs.

    abstract::Stepwise, synthetic alteration of oxytocin, guided by conformational and enzymological considerations, has led to analogs with specifically modified activity profiles and resistance to enzymatic inactivation. General requirements for the design of peptides with therapeutic value are discussed. ...

    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.71.5.1901

    authors: Walter R,Yamanaka T,Sakakibara S

    更新日期:1974-05-01 00:00:00

  • Geoelectric potential changes: possible precursors to earthquakes in Japan.

    abstract::Whether electromagnetic precursors to earthquakes (EQs) exist is an important question not only for EQ prediction but also for understanding the physical processes of EQ generation. Slow transient geoelectric potential changes have been observed before several recent EQs in Japan. In most cases, they appeared 1-19 day...

    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.97.9.4561

    authors: Uyeda S,Nagao T,Orihara Y,Yamaguchi T,Takahashi I

    更新日期:2000-04-25 00:00:00

  • Induction by lithium ion of multiplication of mouse mammary epithelium in culture.

    abstract::Lithium ion at concentrations between 2 and 20 mM simulated the stimulatory effects of insulin on the uptake of alpha-aminoisobutyric acid, synthesis of RNA and DNA, and cell multiplication in mouse mammary gland explants cultured in a chemically defined synthetic medium. Other monovalent cations were virtually ineffe...

    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.76.6.2823

    authors: Hori C,Oka T

    更新日期:1979-06-01 00:00:00

  • Dynamical principles in biological processes: a model of charge migration in proteins and DNA.

    abstract::The generalized master equations (GMEs) that contain multiple time scales have been derived quantum mechanically. The GME method has then been applied to a model of charge migration in proteins that invokes the hole hopping between local amino acid sites driven by the torsional motions of the floppy backbones. This mo...

    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.140196597

    authors: Schlag EW,Yang DY,Sheu SY,Selzle HL,Lin SH,Rentzepis PM

    更新日期:2000-08-29 00:00:00

  • The introduction of RNA-DNA differences underlies interindividual variation in the human IL12RB1 mRNA repertoire.

    abstract::Human interleukin 12 and interleukin 23 (IL12/23) influence susceptibility or resistance to multiple diseases. However, the reasons underlying individual differences in IL12/23 sensitivity remain poorly understood. Here we report that in human peripheral blood mononuclear cells (PBMCs) and inflamed lungs, the majority...

    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.1515978112

    authors: Turner AJ,Aggarwal P,Miller HE,Waukau J,Routes JM,Broeckel U,Robinson RT

    更新日期:2015-12-15 00:00:00

  • Nerve growth factor: activation of the classical complement pathway by specific substitution for component C1-.

    abstract::The interaction of homogeneous preparations of mouse submandibular gland nerve growth factor (NGF) with the classical complement pathway was studied. NGF was found to be capable of carrying out the enzyme activities of the first component (C1-) of the classical complement pathway (i.e., the cleavage of zymogen C4 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.79.8.2519

    authors: Boyle MD,Young M

    更新日期:1982-04-01 00:00:00

  • Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor.

    abstract::The triphenylmethane derivative aurintricarboxylic acid (ATA), but not aurin, selectively prevented the binding of OKT4A/Leu-3a monoclonal antibody (mAb) and, to a lesser extent, OKT4 mAb to the CD4 cell receptor for human immunodeficiency virus type 1 (HIV-1). The effect was seen within 1 min at an ATA concentration ...

    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.86.9.3322

    authors: Schols D,Baba M,Pauwels R,Desmyter J,De Clercq E

    更新日期:1989-05-01 00:00:00

  • Purification and identification of pituitary cytotropic factor.

    abstract::It has been shown that the pituitary contains a cytotropic factor (CTF) that stimulates the secretion of catecholamines by dopaminergic neurons of the hypothalamus. In the present study, CTF was purified from rat pituitaries and found by means of mass spectrometric analysis to be adenosine. This finding was corroborat...

    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.92.12.5351

    authors: Porter JC,Ijames CF,Wang TC,Markey SP

    更新日期:1995-06-06 00:00:00

  • Rapid polyether cleavage via extracellular one-electron oxidation by a brown-rot basidiomycete.

    abstract::Fungi that cause brown rot of wood are essential biomass recyclers and also the principal agents of decay in wooden structures, but the extracellular mechanisms by which they degrade lignocellulose remain unknown. To test the hypothesis that brown-rot fungi use extracellular free radical oxidants as biodegradative too...

    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.95.18.10373

    authors: Kerem Z,Bao W,Hammel KE

    更新日期:1998-09-01 00:00:00

  • Association of microtubules and intermediate filaments in normal fibroblasts and its disruption upon transformation by a temperature-sensitive mutant of Rous sarcoma virus.

    abstract::By double indirect immunofluorescence, using primary rabbit antibodies to tubulin and guinea pig antibodies to vimentin, we have simultaneously labeled microtubules and intermediate filaments in several types of cultured normal fibroblasts. With well-spread interphase cells there was an extensive but not complete corr...

    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.78.11.6986

    authors: Ball EH,Singer SJ

    更新日期:1981-11-01 00:00:00

  • Repression of unconscious information by conscious processing: evidence from affective blindsight induced by transcranial magnetic stimulation.

    abstract::Some patients with a lesion to the primary visual cortex (V1) show "blindsight": the remarkable ability to guess correctly about attributes of stimuli presented to the blind hemifield. Here, we show that blindsight can be induced in normal observers by using transcranial magnetic stimulation of the occipital cortex bu...

    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.0500834102

    authors: Jolij J,Lamme VA

    更新日期:2005-07-26 00:00:00

  • In situ structure and dynamics of DNA origami determined through molecular dynamics simulations.

    abstract::The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic stru...

    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.1316521110

    authors: Yoo J,Aksimentiev A

    更新日期:2013-12-10 00:00:00

  • Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis.

    abstract::Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particula...

    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.1522054113

    authors: Suzuki H,Ito Y,Shinohara M,Yamashita S,Ichinose S,Kishida A,Oyaizu T,Kayama T,Nakamichi R,Koda N,Yagishita K,Lotz MK,Okawa A,Asahara H

    更新日期:2016-07-12 00:00:00

  • Control of ovarian cell growth in culture by serum and pituitary factors.

    abstract::An ovarian cell line was developed that requires hormonal conditioning of the host for growth in vivo and that requires special factors for growth in vitro. It is necessary to prepare special culture media to demonstrate the effects of growth factors in vitro. To this end, methods were developed for removing from seru...

    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.72.2.483

    authors: Nishikawa K,Armelin HA,Sato G

    更新日期:1975-02-01 00:00:00

  • Effects of the peer metagenomic environment on smoking behavior.

    abstract::Recent scholarship suggests that the genomes of those around us affect our own phenotypes. Much of the empirical evidence for such "metagenomic" effects comes from animal studies, where the socio-genetic environment can be easily manipulated. Among humans, it is more difficult to identify such effects given the nonran...

    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.1806901116

    authors: Sotoudeh R,Harris KM,Conley D

    更新日期:2019-08-13 00:00:00

  • Photoaffinity labeling of indole-3-acetic acid-binding proteins in maize.

    abstract::The photoaffinity labeling agent 5-azidoindole-3-acetic acid, an analog of the endogenous plant hormone indole-3-acetic acid (an auxin), was used to identify indole-3-acetic acid-binding proteins in maize. Two peptides with subunit molecular masses of 24 and 22 kilodaltons are specifically labeled in a saturable manne...

    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.86.16.6153

    authors: Jones AM,Venis MA

    更新日期:1989-08-01 00:00:00

  • Prevention of viral-chemical co-carcinogenesis in vitro by type-specific anti-viral antibody.

    abstract::Low passage Fischer rat embryo cultures, which are normally very resistant to transformation by 3-methylcholanthrene but are highly susceptible when chronically infected with the Rauscher murine leukemia virus, were completely protected from transformation by methylcholanthrene when treated with neutralizing antibody ...

    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.73.1.152

    authors: Price PJ,Bellew TM,King MP,Freeman AE,Gilden RV,Huebner RJ

    更新日期:1976-01-01 00:00:00

  • The role of nanostructure in the wetting behavior of mixed-monolayer-protected metal nanoparticles.

    abstract::Self-assembled monolayer-protected nanoparticles are promising candidates for applications, such as sensing and drug delivery, in which the molecular ligands' interactions with the surrounding environment play a crucial role. We recently showed that, when gold nanoparticles are coated with a binary mixture of immiscib...

    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.0803929105

    authors: Centrone A,Penzo E,Sharma M,Myerson JW,Jackson AM,Marzari N,Stellacci F

    更新日期:2008-07-22 00:00:00

  • Facilitating and nonfacilitating synapses on pyramidal cells: a correlation between physiology and morphology.

    abstract::Pyramidal cells in piriform cortex receive excitatory inputs from two different sources that are segregated onto adjacent segments of their apical dendrites. The present studies show that excitatory postsynaptic potentials (EPSPs) evoked by primary olfactory tract afferents that terminate on distal apical segments dis...

    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.83.4.1115

    authors: Bower JM,Haberly LB

    更新日期:1986-02-01 00:00:00

  • Measurements of the concentration and composition of nuclei for cirrus formation.

    abstract::This article addresses the need for new data on indirect effects of natural and anthropogenic aerosol particles on atmospheric ice clouds. Simultaneous measurements of the concentration and composition of tropospheric aerosol particles capable of initiating ice in cold (cirrus) clouds are reported. Measurements suppor...

    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.2532677100

    authors: DeMott PJ,Cziczo DJ,Prenni AJ,Murphy DM,Kreidenweis SM,Thomson DS,Borys R,Rogers DC

    更新日期:2003-12-09 00:00:00

  • Human placental alkaline phosphatase in liver and intestine.

    abstract::Three distinct forms of human alkaline phosphatase, presumably isozymes, are known, each apparently associated with a specific tissue. These are placental, intestinal, and liver (kidney and bone). We have used a specific immunoassay and HPLC to show that placental alkaline phosphatase is also present in extracts of li...

    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.82.18.6080

    authors: Garattini E,Margolis J,Heimer E,Felix A,Udenfriend S

    更新日期:1985-09-01 00:00:00

  • In vitro trimerization of OmpF porin secreted by spheroplasts of Escherichia coli.

    abstract::It is not yet clear how bacterial outer membrane proteins reach their correct destination after they are secreted across the cytoplasmic membrane. We show here that porin OmpF is secreted into the medium as a water-soluble monomeric protein by spheroplasts of Escherichia coli. Furthermore, this monomeric porin is take...

    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.87.2.743

    authors: Sen K,Nikaido H

    更新日期:1990-01-01 00:00:00

  • Analysis of the helical ribosome structures of Mycoplasma gallisepticum.

    abstract::The helical ribosome structures of Mycoplasma gallisepticum have been analyzed by optical diffraction and the rotational symmetry technique. The helix repeat (510 A) is composed of 10 ribosomes in 3 turns. The rotational studies show some ribosome fine structure. ...

    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.68.1.43

    authors: Maniloff J

    更新日期:1971-01-01 00:00:00

  • Tuning and switching a DNA polymerase motor with mechanical tension.

    abstract::Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced "tuning" and "switching." The internal conformational states of the enzyme motor are represented as nodes, and 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.1033134100

    authors: Goel A,Astumian RD,Herschbach D

    更新日期:2003-08-19 00:00:00

  • Protein design algorithms predict viable resistance to an experimental antifolate.

    abstract::Methods to accurately predict potential drug target mutations in response to early-stage leads could drive the design of more resilient first generation drug candidates. In this study, a structure-based protein design algorithm (K* in the OSPREY suite) was used to prospectively identify single-nucleotide polymorphisms...

    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.1411548112

    authors: Reeve SM,Gainza P,Frey KM,Georgiev I,Donald BR,Anderson AC

    更新日期:2015-01-20 00:00:00

  • Wnt signaling interacts with Shh to regulate taste papilla development.

    abstract::Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expre...

    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.0607399104

    authors: Iwatsuki K,Liu HX,Grónder A,Singer MA,Lane TF,Grosschedl R,Mistretta CM,Margolskee RF

    更新日期:2007-02-13 00:00:00

  • Lower bounds to eigenvalues of the Schrödinger equation by solution of a 90-y challenge.

    abstract::The Ritz upper bound to eigenvalues of Hermitian operators is essential for many applications in science. It is a staple of quantum chemistry and physics computations. The lower bound devised by Temple in 1928 [G. Temple, Proc. R. Soc. A Math. Phys. Eng. Sci. 119, 276-293 (1928)] is not, since it converges too slowly....

    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.2007093117

    authors: Martinazzo R,Pollak E

    更新日期:2020-07-14 00:00:00

  • beta-endorphin is a potent analgesic agent.

    abstract::beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its ...

    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.73.8.2895

    authors: Loh HH,Tseng LF,Wei E,Li CH

    更新日期:1976-08-01 00:00:00

  • Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors.

    abstract::This study examines the basis of resistance and sensitivity of normal and transformed cells to histone deacetylase inhibitor (HDACi)-induced cell death, specifically the role of caspases and thioredoxin (Trx). An important attribute of HDACis is that they induce cancer cell death at concentrations to which normal cell...

    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.0408732102

    authors: Ungerstedt JS,Sowa Y,Xu WS,Shao Y,Dokmanovic M,Perez G,Ngo L,Holmgren A,Jiang X,Marks PA

    更新日期:2005-01-18 00:00:00

  • Epistasis in tomato color mutations involves regulation of phytoene synthase 1 expression by cis-carotenoids.

    abstract::Tomato (Solanum lycopersicum) fruit accumulate the red carotenoid pigment lycopene. The recessive mutation yellow-flesh (locus r) in tomato eliminates fruit carotenoids by disrupting the activity of the fruit-specific phytoene synthase (PSY1), the first committed step in the carotenoid biosynthesis pathway. Fruits of ...

    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.1214808109

    authors: Kachanovsky DE,Filler S,Isaacson T,Hirschberg J

    更新日期:2012-11-13 00:00:00