Kinetics of chain motions within a protein-folding intermediate.

Abstract:

:Small proteins can fold remarkably rapidly, even in μs. What limits their rate of folding? The Engrailed homeodomain is a particularly well-characterized example, which folds ultrafast via an intermediate, I, of solved structure. It is a puzzle that the helix2-turn-helix3 motif of the 3-helix bundle forms in approximately 2 μs, but the final docking of preformed helix1 in I requires approximately 20 μs. Simulation and structural data suggest that nonnative interactions may slow down helix docking. Here we report the direct measurement of chain motions in I by using photoinduced electron transfer fluorescence-quenching correlation spectroscopy (PET-FCS). We use a mutant that traps I at physiological ionic strength but refolds at higher ionic strength. A single Trp in helix3 quenches the fluorescence of an extrinsic label on contact with it. We placed the label along the sequence to probe segmental chain motions. At high ionic strength, we found two relaxations for all probed positions on the 2- and 20-μs time scale, corresponding to the known folding processes, and a 200-ns phase attributable to loop closure kinetics in the unfolded state. At low ionic strength, we found only the 2-μs and 200-ns phase for labels in the helix2-turn-helix3 motif of I, because the native state is not significantly populated. But for labels in helix1 we observed an additional approximately 10-μs phase showing that it was moving slowly, with a rate constant similar to that for overall folding under native conditions. Folding was rate-limited by chain motions on a rough energy surface where nonnative interactions constrain motion.

authors

Neuweiler H,Banachewicz W,Fersht AR

doi

10.1073/pnas.1011666107

subject

Has Abstract

pub_date

2010-12-21 00:00:00

pages

22106-10

issue

51

eissn

0027-8424

issn

1091-6490

pii

1011666107

journal_volume

107

pub_type

杂志文章
  • An integral membrane component of coatomer-coated transport vesicles defines a family of proteins involved in budding.

    abstract::We have isolated a major integral membrane protein from Golgi-derived coatomer-coated vesicles. This 24-kDa protein, p24, defines a family of integral membrane proteins with homologs present in yeast and humans. In addition to sequence similarity, all p24 family members contain a motif with the characteristic heptad 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.92.17.8011

    authors: Stamnes MA,Craighead MW,Hoe MH,Lampen N,Geromanos S,Tempst P,Rothman JE

    更新日期:1995-08-15 00:00:00

  • Identification of direct residue contacts in protein-protein interaction by message passing.

    abstract::Understanding the molecular determinants of specificity in protein-protein interaction is an outstanding challenge of postgenome biology. The availability of large protein databases generated from sequences of hundreds of bacterial genomes enables various statistical approaches to this problem. In this context covaria...

    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.0805923106

    authors: Weigt M,White RA,Szurmant H,Hoch JA,Hwa T

    更新日期:2009-01-06 00:00:00

  • Prediction of protein folding class using global description of amino acid sequence.

    abstract::We present a method for predicting protein folding class based on global protein chain description and a voting process. Selection of the best descriptors was achieved by a computer-simulated neural network trained on a data base consisting of 83 folding classes. Protein-chain descriptors include overall composition, ...

    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.92.19.8700

    authors: Dubchak I,Muchnik I,Holbrook SR,Kim SH

    更新日期:1995-09-12 00:00:00

  • Identification of anthrax toxin genes in a Bacillus cereus associated with an illness resembling inhalation anthrax.

    abstract::Bacillus anthracis is the etiologic agent of anthrax, an acute fatal disease among mammals. It was thought to differ from Bacillus cereus, an opportunistic pathogen and cause of food poisoning, by the presence of plasmids pXO1 and pXO2, which encode the lethal toxin complex and the poly-gamma-d-glutamic acid capsule, ...

    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.0402414101

    authors: Hoffmaster AR,Ravel J,Rasko DA,Chapman GD,Chute MD,Marston CK,De BK,Sacchi CT,Fitzgerald C,Mayer LW,Maiden MC,Priest FG,Barker M,Jiang L,Cer RZ,Rilstone J,Peterson SN,Weyant RS,Galloway DR,Read TD,Popovic T,Fras

    更新日期:2004-06-01 00:00:00

  • Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

    abstract::In the retinae of many vertebrates, there are classes of horizontal cell that probably utilize gamma-aminobutyric acid (GABA) as a neurotransmitter. As with other amino acid transmitter agents, the postsynaptic action of GABA is thought to be terminated by uptake into neurons and glia surrounding the release site. 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.87.22.8945

    authors: Malchow RP,Ripps H

    更新日期:1990-11-01 00:00:00

  • Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse.

    abstract::Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the 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.0402511101

    authors: Ueki K,Kondo T,Tseng YH,Kahn CR

    更新日期:2004-07-13 00:00:00

  • Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air.

    abstract::There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO(2) inhalation. Comparis...

    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.98.4.2029

    authors: Brannan S,Liotti M,Egan G,Shade R,Madden L,Robillard R,Abplanalp B,Stofer K,Denton D,Fox PT

    更新日期:2001-02-13 00:00:00

  • Sinuous flow in metals.

    abstract::Annealed metals are surprisingly difficult to cut, involving high forces and an unusually thick "chip." This anomaly has long been explained, based on ex situ observations, using a model of smooth plastic flow with uniform shear to describe material removal by chip formation. Here we show that this phenomenon is actua...

    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.1509165112

    authors: Yeung H,Viswanathan K,Compton WD,Chandrasekar S

    更新日期:2015-08-11 00:00:00

  • An artificial cell-cycle inhibitor isolated from a combinatorial library.

    abstract::Understanding the genetic networks that operate inside cells will require the dissection of interactions among network members. Here we describe a peptide aptamer isolated from a combinatorial library that distinguishes among such interactions. This aptamer binds to cyclin-dependent kinase 2 (Cdk2) and inhibits its ki...

    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.95.24.14272

    authors: Cohen BA,Colas P,Brent R

    更新日期:1998-11-24 00:00:00

  • Large-scale evidence of dependency length minimization in 37 languages.

    abstract::Explaining the variation between human languages and the constraints on that variation is a core goal of linguistics. In the last 20 y, it has been claimed that many striking universals of cross-linguistic variation follow from a hypothetical principle that dependency length--the distance between syntactically related...

    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.1502134112

    authors: Futrell R,Mahowald K,Gibson E

    更新日期:2015-08-18 00:00:00

  • A G protein-coupled receptor with low density lipoprotein-binding motifs suggests a role for lipoproteins in G-linked signal transduction.

    abstract::We have isolated and analyzed a cDNA from the central nervous system of the mollusc Lymnaea stagnalis encoding a putative receptor, which might be a natural hybrid between two different classes of receptor proteins. Preceded by a signal peptide, two types of repeated sequences are present in the N-terminal part of 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.91.11.4816

    authors: Tensen CP,Van Kesteren ER,Planta RJ,Cox KJ,Burke JF,van Heerikhuizen H,Vreugdenhil E

    更新日期:1994-05-24 00:00:00

  • CDK8/19 Mediator kinases potentiate induction of transcription by NFκB.

    abstract::The nuclear factor-κB (NFκB) family of transcription factors has been implicated in inflammatory disorders, viral infections, and cancer. Most of the drugs that inhibit NFκB show significant side effects, possibly due to sustained NFκB suppression. Drugs affecting induced, but not basal, NFκB activity may have the pot...

    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.1710467114

    authors: Chen M,Liang J,Ji H,Yang Z,Altilia S,Hu B,Schronce A,McDermott MSJ,Schools GP,Lim CU,Oliver D,Shtutman MS,Lu T,Stark GR,Porter DC,Broude EV,Roninson IB

    更新日期:2017-09-19 00:00:00

  • Changes in hepatic messenger RNA for phosphoenolpyruvate carboxykinase (GTP) during development.

    abstract::Phosphoenolpyruvate carboxykinase (GTP) [GTP;oxaloacetate carboxy-lyase(transphosphorylating); EC 4.1.1.32] is absent in rat liver cytosol during fetal life and is synthesized initially at birth. De novo synthesis of the enzyme can be induced prematurely by injection of dibutyryl cyclic AMP or glucagon into fetal anim...

    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.75.9.4189

    authors: Garcia Ruiz JP,Ingram R,Hanson RW

    更新日期:1978-09-01 00:00:00

  • The wisdom of crowds for visual search.

    abstract::Decision-making accuracy typically increases through collective integration of people's judgments into group decisions, a phenomenon known as the wisdom of crowds. For simple perceptual laboratory tasks, classic signal detection theory specifies the upper limit for collective integration benefits obtained by weighted ...

    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.1610732114

    authors: Juni MZ,Eckstein MP

    更新日期:2017-05-23 00:00:00

  • Synthesis of nuclear proteins during DNA repair synthesis in human diploid fibroblasts damaged with ultraviolet radiation of N-acetoxy-2-acetylaminofluroene.

    abstract::We have examined the accumulation of newly synthesized nuclear proteins into nuclei during DNA repair synthesis in confluent WI-38 human diploid fibroblasts damaged with ultraviolet radiation or N-acetoxy-2-acetylaminofluroene. In contrast to a marked stimulation of DNA repair synthesis, stimulation of amino acid inco...

    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.73.5.1466

    authors: Stein GS,Park WD,Stein JL,Lieberman MW

    更新日期:1976-05-01 00:00:00

  • Thy-1: a differentiation marker of potential mammary myoepithelial cells in vitro.

    abstract::The rat mammary cell line Rama 25 [Bennett, D.C., Peachey, L.A., Durbin, H. & Rudland, P.S. (1978) Cell 15, 283--298] differentiates morphologically in vitro from a cuboidal form to a fusiform cell resembling myoepithelial cells. This differentiation occurs in all clonal isolates of the line. By using three different ...

    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.75.12.6093

    authors: Lennon VA,Unger M,Dulbecco R

    更新日期:1978-12-01 00:00:00

  • Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes.

    abstract::Vaccination has been used to control the spread of seasonal flu; however, the virus continues to evolve and escape from host immune response through mutation and increasing glycosylation. Efforts have been directed toward development of a universal vaccine with broadly protective activity against multiple influenza st...

    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.2004783117

    authors: Liao HY,Wang SC,Ko YA,Lin KI,Ma C,Cheng TR,Wong CH

    更新日期:2020-07-28 00:00:00

  • Interaction between VPS35 and RABG3f is necessary as a checkpoint to control fusion of late compartments with the vacuole.

    abstract::Vacuoles are essential organelles in plants, playing crucial roles, such as cellular material degradation, ion and metabolite storage, and turgor maintenance. Vacuoles receive material via the endocytic, secretory, and autophagic pathways. Membrane fusion is the last step during which prevacuolar compartments (PVCs) a...

    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.1905321116

    authors: Rodriguez-Furlan C,Domozych D,Qian W,Enquist PA,Li X,Zhang C,Schenk R,Winbigler HS,Jackson W,Raikhel NV,Hicks GR

    更新日期:2019-10-15 00:00:00

  • Biological transport processes and space dimension.

    abstract::We discuss the generic time behavior of reaction-diffusion processes capable of modeling various types of biological transport processes, such as ligand migration in proteins and gating fluctuations in ion channel proteins. The main observable in these two cases, the fraction of unbound ligands and the probability 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.88.15.6750

    authors: Nadler W,Stein DL

    更新日期:1991-08-01 00:00:00

  • Identification of a site on 23S ribosomal RNA located at the peptidyl transferase center.

    abstract::3-(4'-Benzoylphenyl)propionyl[3H] Phe-tRNA bound to the peptidyl site of the ribosome is photo-crosslinked exclusively to 23S RNA on irradiation at 320 nm. The site of reaction has been identified both by hybridization and primer-extension experiments as uridine-2584 and uridine-2585, located within the central loop o...

    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.81.12.3607

    authors: Barta A,Steiner G,Brosius J,Noller HF,Kuechler E

    更新日期:1984-06-01 00:00:00

  • The nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias.

    abstract::Genomic and cDNA clones for the human nerve growth factor receptor have been used in conjunction with somatic cell hybrid analysis and in situ hybridization to localize the nerve growth factor receptor locus to human chromosome region 17q12-q22. Additionally, part, if not all, of the nerve growth factor receptor locus...

    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.83.5.1403

    authors: Huebner K,Isobe M,Chao M,Bothwell M,Ross AH,Finan J,Hoxie JA,Sehgal A,Buck CR,Lanahan A

    更新日期:1986-03-01 00:00:00

  • CYLD regulates spindle orientation by stabilizing astral microtubules and promoting dishevelled-NuMA-dynein/dynactin complex formation.

    abstract::Oriented cell division is critical for cell fate specification, tissue organization, and tissue homeostasis, and relies on proper orientation of the mitotic spindle. The molecular mechanisms underlying the regulation of spindle orientation remain largely unknown. Herein, we identify a critical role for cylindromatosis...

    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.1319341111

    authors: Yang Y,Liu M,Li D,Ran J,Gao J,Suo S,Sun SC,Zhou J

    更新日期:2014-02-11 00:00:00

  • The energetic cost of domain reorientation in maltose-binding protein as studied by NMR and fluorescence spectroscopy.

    abstract::Maltose-binding protein (MBP) is a two-domain protein that undergoes a ligand-mediated conformational rearrangement from an "open" to a "closed" structure on binding to maltooligosaccharides. To characterize the energy landscape associated with this transition, we have generated five variants of MBP with mutations loc...

    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.2134311100

    authors: Millet O,Hudson RP,Kay LE

    更新日期:2003-10-28 00:00:00

  • Evolution of green plants as deduced from 5S rRNA sequences.

    abstract::We have constructed a phylogenic tree for green plants by comparing 5S rRNA sequences. The tree suggests that the emergence of most of the uni- and multicellular green algae such as Chlamydomonas, Spirogyra, Ulva, and Chlorella occurred in the early stage of green plant evolution. The branching point of Nitella is a l...

    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.82.3.820

    authors: Hori H,Lim BL,Osawa S

    更新日期:1985-02-01 00:00:00

  • Nucleotide sequence of the 3' region of an infectious human T-cell leukemia virus type II genome.

    abstract::The nucleic acid sequence of the 3' region of human T-cell leukemia virus type II (HTLV-II) proviral DNA was determined using a HTLV-II proviral clone that could be recovered as infectious, transforming virus. The sequence data indicate a region of unknown function of approximately equal to 1.6 kilobase pairs in the 3...

    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.81.21.6657

    authors: Shimotohno K,Wachsman W,Takahashi Y,Golde DW,Miwa M,Sugimura T,Chen IS

    更新日期:1984-11-01 00:00:00

  • A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase.

    abstract::Modifier screens have been powerful genetic tools to define signaling pathways in lower organisms. The identification of modifier loci in mice has begun to allow a similar dissection of mammalian signaling pathways. Transgenic mice (Btk(lo)) expressing 25% of endogenous levels of Bruton's tyrosine kinase (Btk) have B ...

    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.110146697

    authors: Satterthwaite AB,Willis F,Kanchanastit P,Fruman D,Cantley LC,Helgason CD,Humphries RK,Lowell CA,Simon M,Leitges M,Tarakhovsky A,Tedder TF,Lesche R,Wu H,Witte ON

    更新日期:2000-06-06 00:00:00

  • Structure and function of bacterial ribosomes. XI. Dependence of 50S ribosomal assembly on simultaneous assembly of 30S subunits.

    abstract::Some spectinomycin-resistant mutants of Escherichia coli are cold-sensitive. They are unable to assemble both 30S and 50S ribosomal subunits at low temperatures. They accumulate two kinds of incomplete particles, related to 30S and 50S subunits respectively. A single mutation, causing an alteration in a 30S ribosomal ...

    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.67.3.1440

    authors: Nashimoto H,Nomura M

    更新日期:1970-11-01 00:00:00

  • Purification and characterization of the DNA polymerase of human breast cancer particles.

    abstract::Previous studies have identified human breast tumor particles possessing many of the features characteristic of RNA tumor viruses. In addition to the expected size (600 S) and density (1.16 g/ml) these include possession of an outer membrane and an inner one surrounding a "core" containing a DNA polymerase and a large...

    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.74.2.764

    authors: Ohno T,Sweet RW,Dejak D,Spiegelman S

    更新日期:1977-02-01 00:00:00

  • Reduced fitness in progeny from old parents in a natural population.

    abstract::A nongenetic, transgenerational effect of parental age on offspring fitness has been described in many taxa in the laboratory. Such a transgenerational fitness effect will have important influences on population dynamics, population age structure, and the evolution of aging and lifespan. However, effects of parental a...

    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.1422715112

    authors: Schroeder J,Nakagawa S,Rees M,Mannarelli ME,Burke T

    更新日期:2015-03-31 00:00:00

  • Infection of rabbit T-cell and macrophage lines with human immunodeficiency virus.

    abstract::We report the successful infection of two rabbit T-cell lines and one rabbit macrophage line with human immunodeficiency virus 1 (HIV-1). One T-cell line was a herpesvirus ateles transformant, the other T-cell line was a human T-cell leukemia virus I transformant, and the macrophage line was a simian virus 40 transfor...

    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.85.12.4455

    authors: Kulaga H,Folks TM,Rutledge R,Kindt TJ

    更新日期:1988-06-01 00:00:00