Abstract:
:Natively unfolded proteins play key roles in normal and pathological biochemical processes. Despite their importance for function, this category of proteins remains beyond the reach of classical structural biology because of their inherent conformational heterogeneity. We present a description of the intrinsic conformational sampling of unfolded proteins based on residue-specific /Psi propensities from loop regions of a folded protein database and simple volume exclusion. This approach is used to propose a structural model of the 57-aa, natively disordered region of the nucleocapsid-binding domain of Sendai virus phosphoprotein. Structural ensembles obeying these simple rules of conformational sampling are used to simulate averaged residual dipolar couplings (RDCs) and small-angle x-ray scattering data. This protein is particularly informative because RDC data from the equally sized folded and unfolded domains both report on the unstructured region, allowing a quantitative analysis of the degree of order present in this part of the protein. Close agreement between experimental and simulated RDC and small-angle x-ray scattering data validates this simple model of conformational sampling, providing a precise description of local structure and dynamics and average dimensions of the ensemble of sampled structures. RDC data from two urea-unfolded systems are also closely reproduced. The demonstration that conformational behavior of unfolded proteins can be accurately predicted from the primary sequence by using a simple set of rules has important consequences for our understanding of the structure and dynamics of the unstructured state.
journal_name
Proc Natl Acad Sci U S Aauthors
Bernadó P,Blanchard L,Timmins P,Marion D,Ruigrok RW,Blackledge Mdoi
10.1073/pnas.0506202102keywords:
subject
Has Abstractpub_date
2005-11-22 00:00:00pages
17002-7issue
47eissn
0027-8424issn
1091-6490pii
0506202102journal_volume
102pub_type
杂志文章abstract::Hereditary hemochromatosis (HH) is a common autosomal recessive disorder of iron metabolism that leads to excessive iron storage in the liver and other organs. Recently, between 83 and 100% of HH patients have been found to be homozygous for the same mutation in a novel major histocompatibility complex class I-like ge...
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.94.6.2534
更新日期:1997-03-18 00:00:00
abstract::Many ion channels exhibit a slow stochastic switching between distinct modes of gating activity. This feature of channel behavior has pronounced implications for the dynamics of ionic currents and the signaling pathways that they regulate. A canonical example is the inositol 1,4,5-trisphosphate receptor (IP3R) channel...
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.1604090113
更新日期:2016-09-06 00:00:00
abstract::Small, single-module proteins that fold in a single cooperative step may be paradigms for understanding early events in protein-folding pathways generally. Recent experimental studies of the 64-residue chymotrypsin inhibitor 2 (CI2) support a nucleation mechanism for folding, as do some computer stimulations. CI2 has ...
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.92.24.10869
更新日期:1995-11-21 00:00:00
abstract::We examined the effect of the inhibition of initiation of DNA replication on the membrane association of the chromosomal origin of replication of Bacillus subtilis and the Staphylococcus aureus-Bacillus pumilus chimeric plasmid pSL103, using temperature-sensitive mutants of B. subtilis that have specifically affected ...
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.77.5.2834
更新日期:1980-05-01 00:00:00
abstract::We use sequential large-scale crawl data to empirically investigate and validate the dynamics that underlie the evolution of the structure of the web. We find that the overall structure of the web is defined by an intricate interplay between experience or entitlement of the pages (as measured by the number of inbound ...
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.0805921105
更新日期:2008-09-16 00:00:00
abstract::Evidence is presented for two natural transcription initiators positioned internally in the histidine operon of Salmonella typhimurium. They were detected using highly polar S. typhimurium his mutants as recipients for F' Escherichia coli his episomes. These intergeneric complementation tests provide a sensitive metho...
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.65.4.925
更新日期:1970-04-01 00:00:00
abstract::A fraction of mouse RNA containing messenger RNA coding for mouse interferon was translated with high efficiency in a wheat germ system into a fully active product. This product fulfills the criteria for mouse interferon, namely: (1) it was active against vesicular stomatitis virus and herpes simplex virus in mouse ce...
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.72.10.3975
更新日期:1975-10-01 00:00:00
abstract::We have compared the efficiency of transformation by linear DNA fragments in yeast strains carrying different numbers of homologous targets for recombination. In strains carrying dispersed copies of a target and in strains carrying tandem arrays, the frequency of transformation is proportional to the number of targets...
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.91.1.177
更新日期:1994-01-04 00:00:00
abstract::Purified preparations of rabbit skeletal white, red, and cardiac muscle myosin (WM, RM, and CM) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Significant differences in both the molecular weights and number of light chains in these myosins were found. WM has three distinct light-chain co...
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.68.5.946
更新日期:1971-05-01 00:00:00
abstract::To differentiate roles of androgen receptor (AR) in prostate stromal and epithelial cells, we have generated inducible-(ind)ARKO-TRAMP and prostate epithelial-specific ARKO TRAMP (pes-ARKO-TRAMP) mouse models, in which the AR was knocked down in both prostate epithelium and stroma or was knocked out in the prostate ep...
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.0804701105
更新日期:2008-08-26 00:00:00
abstract::Stearic acid is toxic for T lymphocytes in vitro but has little effect on B lymphocytes. To investigate the molecular basis for this difference, purified murine T and B lymphocytes were compared for their abilities to incorporate and metabolize stearic acid. Unstimulated T and B cells incorporated identical amounts 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.86.16.6133
更新日期:1989-08-01 00:00:00
abstract::Conjugative relaxases are the proteins that initiate bacterial conjugation by a site-specific cleavage of the transferred DNA strand. In vitro, they show strand-transferase activity on single-stranded DNA, which suggests they may also be responsible for recircularization of the transferred DNA. In this work, we show t...
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.0506081102
更新日期:2005-11-08 00:00:00
abstract::Most HLA haplotypes carry two expressed DR beta-chain genes; in the DR4 haplotype, the polymorphic locus has been called DR beta 1 and the apparently nonpolymorphic locus has been called DR beta 2. We have isolated nearly full-length DR beta-chain cDNA clones representing each of these two loci from a cell line homozy...
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.84.1.209
更新日期:1987-01-01 00:00:00
abstract::Leukemia cell lines of the monocytic series (HL-60, U-937, and P388D1) produce a hepatocyte-stimulating factor (HSF) following induction of differentiation with phorbol diester. In 24-72 hr, these leukemia cells produce 2-30% the amount of HSF as human peripheral blood monocytes. Cells of the series at earlier stages ...
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.82.5.1443
更新日期:1985-03-01 00:00:00
abstract::A genomic clone coding for the alpha subunit of the mouse complement receptor type 3 and the cellular adhesion molecule Mac-1 has been isolated directly from a genomic library using synthetic oligonucleotide probes based on the amino-terminal amino acid sequence of the protein. The identity of the clone has been estab...
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.83.15.5644
更新日期:1986-08-01 00:00:00
abstract::A key functional event in eukaryotic gene activation is the formation of dynamic protein-protein interaction networks between transcriptional activators and transcriptional coactivators. Seemingly incongruent with the tight regulation of transcription, many biochemical and biophysical studies suggest that activators u...
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.2013244117
更新日期:2020-11-03 00:00:00
abstract::S-nitrosation is a posttranslational, oxidative addition of NO to cysteine residues of proteins that has been proposed as a cGMP-independent signaling pathway [Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Nat Rev Mol Cell Biol 6:150-166]. A paradox of S-nitrosation is that only a small set of reactive ...
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.0704898104
更新日期:2007-07-10 00:00:00
abstract::The uterine epithelium of mice and humans undergoes cyclical waves of cell proliferation and differentiation under the regulation of estradiol-17β (E2) and progesterone (P4). These epithelial cells respond to E2 with increased protein and DNA synthesis, whereas P4 inhibits only the E2-induced DNA synthetic response. H...
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.1418973112
更新日期:2015-03-17 00:00:00
abstract::Social bees harbor a simple and specialized microbiota that is spatially organized into different gut compartments. Recent results on the potential involvement of bee gut communities in pathogen protection and nutritional function have drawn attention to the impact of the microbiota on bee health. However, the contrib...
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.1701819114
更新日期:2017-05-02 00:00:00
abstract::Genetic manipulation of nitrogenase and key glutamate-forming enzymes can provide mutants that excrete fixed N2 as NH4+. A derepressed N2 fxation mutant (SK-24) has been isolated , which excretes up to 20.2 mumol of fixed N2 as NH4+ per mg of cell protein in 24 hr at room temperature. Biochemical analysis shows that t...
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.72.1.136
更新日期:1975-01-01 00:00:00
abstract::Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs. TPMT genetic polymorphisms represent a striking example of the potential clinical value of pharmacogenetics. Subjects homozygous for TPMT*3A, the most common variant allele for low activity, an allele that encodes a protein with two...
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.0502352102
更新日期:2005-06-28 00:00:00
abstract::Wnt signaling is required for the maintenance of intestinal stem cells and self-renewal of the intestinal epithelium. Intestinal cancers are frequently associated with mutations that activate the Wnt pathway. The role of Wnt signaling on differentiation of lineage-specific precursors in the intestine is not well chara...
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.0702665104
更新日期:2007-07-03 00:00:00
abstract::OspA (outer surface protein A) is an abundant immunogenic lipoprotein of the Lyme disease spirochete Borrelia burgdorferi. The crystal structure of a soluble recombinant form of OspA was solved in a complex with the Fab fragment of mouse monoclonal antibody 184.1 and refined to a resolution of 1.9 A. OspA has a repeti...
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.94.8.3584
更新日期:1997-04-15 00:00:00
abstract::Although genetic analysis has demonstrated that members of the winged helix, or forkhead, family of transcription factors play pivotal roles in the regulation of cellular differentiation and proliferation, both during development and in the adult, little is known of the mechanisms underlying their regulation. Here we ...
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.96.13.7421
更新日期:1999-06-22 00:00:00
abstract::Biosynthesis of sucrose-6-P catalyzed by sucrose-phosphate synthase (SPS), and the presence of sucrose-phosphate phosphatase (SPP) leading to the formation of sucrose, have both been ascertained in a prokaryotic organism: Anabaena 7119, a filamentous heterocystic cyanobacterium. Two SPS activities (SPS-I and SPS-II) w...
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.93.24.13600
更新日期:1996-11-26 00:00:00
abstract::Double-strand breaks (DSBs) in DNA are lethal unless repaired. Faithful repair requires processing of the DSB ends and interaction with intact homologous DNA, which can produce genetic recombinants. To determine the role of nucleases in DSB end-processing and joint molecule resolution, we studied recombination at 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.0902793106
更新日期:2009-06-09 00:00:00
abstract::BHK cells were inoculated sparsely on one face ("sparse- or s-face") of a thin glass film whose opposite face was covered with a 2- to 3-day-old confluent layer of BHK cells ("confluent- or c-face"). After 7 hr of attaching and spreading in the absence of visible light, most of the cells on the s-face traversed with t...
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.89.17.8288
更新日期:1992-09-01 00:00:00
abstract::Nitric oxide (NO), synthesized from L-arginine by NO synthases (NOS), plays an essential role in the regulation of cerebrovascular tone. Adenoviral vectors have been widely used to transfer recombinant genes to different vascular beds. To determine whether the recombinant endothelial NOS (eNOS) gene can be delivered i...
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.94.23.12568
更新日期:1997-11-11 00:00:00
abstract::Tobacco mosaic virus (TMV) was reconstituted from the RNA of a common strain (OM) and the protein of a watermelon strain of cucumber green mottle mosaic virus (CGMMV-W), which is a member of the tobamovirus group. In 0.25 M phosphate buffer at 25 degrees C, CGMMV-W protein existed mainly as 21S aggregates. When this 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.79.19.5833
更新日期:1982-10-01 00:00:00
abstract::Multiple resistance and pH adaptation (Mrp) complexes are sophisticated cation/proton exchangers found in a vast variety of alkaliphilic and/or halophilic microorganisms, and are critical for their survival in highly challenging environments. This family of antiporters is likely to represent the ancestor of cation pum...
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.2006276117
更新日期:2020-12-08 00:00:00