Abstract:
:Prions are mammalian proteins (PrPs) with a unique pathogenic property: a nonendogenous isoform PrP(Sc) can catalyze conversion of the endogenous PrP(C) isoform into additional PrP(Sc). In this work, we demonstrate that PrP(C) helix 1 has certain properties (hydrophilicity, charge distribution) that make it unique among all naturally occurring alpha-helices, and which are indicative of a highly specific model of prion infectivity. The beta-nucleation model proposes that PrP(Sc) is an aggregate with a hydrophilic core, consisting of a beta-sheet-like arrangement of constituent helix 1 components. It is suggested by using structural arguments, and confirmed by using CHARMM energy calculations, that aggregate formation from two PrP(C) molecules is highly unfavorable, but the addition of chains to an existing aggregate is favorable. The beta-nucleation model is shown to be consistent with the prion species-barrier, as well as with infectivity data. Sequence analysis of all known protein structures indicates that PrP is uniquely suited to beta-nucleation, in contrast to the many proteins that readily form less favorable (often nonspecific) hydrophobic aggregates.
journal_name
Proc Natl Acad Sci U S Aauthors
Morrissey MP,Shakhnovich EIdoi
10.1073/pnas.96.20.11293keywords:
subject
Has Abstractpub_date
1999-09-28 00:00:00pages
11293-8issue
20eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::The extracellular hemoglobin of Ascaris has an extremely high oxygen affinity (P50 = 0.004 mmHg). It consists of eight identical subunits of molecular weight 40,600. Their sequence, determined by protein chemistry, shows two tandemly linked globin-like sequences and an 18-residue C-terminal extension. Two N-linked gly...
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.89.10.4638
更新日期:1992-05-15 00:00:00
abstract::Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable wi...
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.1621375114
更新日期:2017-05-02 00:00:00
abstract::Trisomy is a genetic abnormality of considerable medical importance. The most familiar example is trisomy 21, which causes Down Syndrome [Cummings, M. R. (1988) Human Heredity: Principles and Issues (West Publishing Company, New York)]. In a classic paper, Axelrod and Hamilton [Axelrod, R. & Hamilton, W. D. (1981) Sci...
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.95.5.2361
更新日期:1998-03-03 00:00:00
abstract::Merkel cell polyomavirus (MCV) contributes to approximately 80% of all Merkel cell carcinomas (MCCs), a highly aggressive neuroendocrine carcinoma of the skin. MCV-positive MCC expresses small T antigen (ST) and a truncated form of large T antigen (LT) and usually contains wild-type p53 (TP53) and RB (RB1). In contras...
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.1818798116
更新日期:2019-01-15 00:00:00
abstract::Analysis of the nucleotide and deduced amino acid sequences of the biologically active mouse mdr1 cDNA clone indicates that the protein is formed by two highly homologous halves, each containing six putative transmembrane domains and a nucleotide-binding site. The duplicated unit shows high sequence homology to the pr...
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.86.17.6488
更新日期:1989-09-01 00:00:00
abstract::Several lines of investigation suggest that the nondegradable fluorophores that accumulate as lipofuscin in retinal pigment epithelium (RPE) cells contribute to the etiology of macular degeneration. Despite evidence that much of this fluorescent material may originate as inadvertent products of the retinoid cycle, 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.0501266102
更新日期:2005-05-17 00:00:00
abstract::The genetic code in a eukaryotic system has been expanded by the engineering of Escherichia coli tyrosyl-tRNA synthetase (TyrRS) with the Y37V and Q195C mutations (37V195C), which specifically recognize 3-iodo-L-tyrosine rather than L-tyrosine. In the present study, we determined the 3-iodo-L-tyrosine- and L-tyrosine-...
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.0407039102
更新日期:2005-02-01 00:00:00
abstract::To attempt to locate functionally important regions of the interferon (IFN) molecule, recombinant human IFN-alpha 2 was subjected to proteolytic digestion. The bacterial proteinase thermolysin produced two major complementary fragments, HuIFN-alpha 2-(1-110) and HuIFN-alpha 2-(111-153). After reduction with 2-mercapto...
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.81.4.1045
更新日期:1984-02-01 00:00:00
abstract::The lentiviruses are associated with a wide range of chronic diseases in mammals. These include immunodeficiencies (such as HIV/AIDS in humans), malignancies, and lymphatic and neurological disorders in primates, felids, and a variety of wild and domesticated ungulates. Evolutionary analyses of the genomic sequences 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.0700471104
更新日期:2007-04-10 00:00:00
abstract::Protein 2.1 is a 210-kilodalton protein that connects erythrocyte spectrin to the NH2-terminal cytoplasmic domain of band 3 and thereby functions as the essential linkage between the membrane skeleton and the bilayer. We cleaved this protein into specific chemical domains by limited digestion with trypsin and alpha-ch...
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.81.13.4095
更新日期:1984-07-01 00:00:00
abstract::A longstanding problem in the social, biological, and computational sciences is to determine how groups of distributed individuals can form intelligent collective judgments. Since Galton's discovery of the "wisdom of crowds" [Galton F (1907) Nature 75:450-451], theories of collective intelligence have suggested that t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1615978114
更新日期:2017-06-27 00:00:00
abstract::Helodermin is a vasoactive intestinal peptide-like peptide in the salivary gland venom of the lizard Heloderma suspectum. Helodermin-like immunofluorescence was observed in the parafollicular (C) cells in several mammals and in the C cell homologues of the chicken ultimobranchial gland. Thus, helodermin-like peptides ...
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.86.4.1357
更新日期:1989-02-01 00:00:00
abstract::Telomerase is a special reverse transcriptase that extends one strand of the telomere repeat by using a template embedded in an RNA subunit. Like other polymerases, telomerase is believed to use a pair of divalent metal ions (coordinated by a triad of aspartic acid residues) for catalyzing nucleotide addition. 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.0502252102
更新日期:2005-07-12 00:00:00
abstract::Lampreys are one of the two surviving jawless vertebrate groups and one of a few vertebrate groups with the best exemplified metamorphosis during their life cycle, which consists of a long-lasting larval stage, a peculiar metamorphosis, and a relatively short adulthood with a markedly different anatomy. Although the 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.1415716111
更新日期:2014-10-28 00:00:00
abstract::Infectious tolerance describes the process of CD4(+) regulatory T cells (Tregs) converting naïve T cells to become additional Tregs. We show that antigen-specific Tregs induce, within skin grafts and dendritic cells, the expression of enzymes that consume at least 5 different essential amino acids (EAAs). T cells fail...
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.0903919106
更新日期:2009-07-21 00:00:00
abstract::DNA hybridization was used to compare representatives of the major groups of marsupials and a eutherian outgroup. Because of the large genetic distances separating marsupial families, trees were calculated from normalized percentages of hybridization; thermal-melting statistics, however, gave identical topologies for ...
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.88.23.10465
更新日期:1991-12-01 00:00:00
abstract::Continuous and intensive exploitation of wildlife resources by early agricultural societies had major ecological consequences in the ancient Near East. In particular, hunting strategies of post-Neolithic societies involving the mass killing of wild ungulates contributed to the eventual extirpation of a number of wild ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1017647108
更新日期:2011-05-03 00:00:00
abstract::Adenosine, dibutyryl cyclic AMP, monobutyryl cyclic AMP, cyclic AMP, and 5'-AMP have a remarkable morphogenetic effect on cultured iris epithelial cells obtained from adult newt. They alter the broad undulating membrane of the cell into branching strands of cytoplasm, a configuration that has been named "stellate." Th...
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.70.8.2286
更新日期:1973-08-01 00:00:00
abstract::The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution of Wnts to the development of ventral midbrain (VM) dopaminergic (DA) neurons. Our results show that beta-catenin is expressed in DA precursor cells and that beta-cat...
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.1534900100
更新日期:2003-10-28 00:00:00
abstract::We have studied the expression of simian virus 40 (SV40) specific tumor antigen (T-antigen) and viral RNA in SV40-transformed mouse 3T3 cells that are temperature-sensitive for the expression of the transformed phenotype (ts SV3T3). Although transformed by wild-type SV40, ts SV3T3 cells at 32 degrees behave like stand...
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.73.6.1931
更新日期:1976-06-01 00:00:00
abstract::Most human tumors are clonal in origin, although the cells may be diverse in their properties. Since the tumors evolve through progressive stages over decades of time, it is possible that the conditions that induced the tumor transform many cells, but that selective overgrowth of the fastest growing lead to a clonal 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.90.22.10524
更新日期:1993-11-15 00:00:00
abstract::The Xlim-1 gene is activated in the late blastula stage of Xenopus embryogenesis in the mesoderm, and its RNA product becomes concentrated in the Spemann organizer at early gastrula stage. A major regulator of early expression of Xlim-1 is activin or an activin-like signal. We report experiments aiming to identify 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.94.18.9717
更新日期:1997-09-02 00:00:00
abstract::Staphylococcus aureus is a leading cause of both nosocomial and community-acquired infection. Biofilm formation at the site of infection reduces antimicrobial susceptibility and can lead to chronic infection. During biofilm formation, a subset of cells liberate cytoplasmic proteins and DNA, which are repurposed to for...
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.1704544114
更新日期:2017-07-18 00:00:00
abstract::We have previously identified a generally occurring short-range mobility of nucleosome cores on DNA in relatively low ionic strength conditions. Here we report that this mobility of histone octamers positioned on constructs of 5S rDNA is suppressed by the binding of histone H1 or H5 to the nucleosome. Histone H5 is th...
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.91.22.10275
更新日期:1994-10-25 00:00:00
abstract::Ethylenediaminetetraacetate and other divalent-cation-complexing agents greatly stimulate the cellular binding of DNA molecules to competent pneumococci, while the appearance of genetic transformants and nuclease-resistant DNA binding are completely inhibited. Based on this finding, we developed an experimental system...
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.71.4.1493
更新日期:1974-04-01 00:00:00
abstract::Whereas several apoptosis-related proteins have been linked to the antiapoptotic effects of Akt serine-threonine kinase, the search continues to explain the Akt signaling role in promoting cell survival via antiapoptotic effects. Here, we demonstrate that Akt phosphorylates the androgen receptor (AR) at Ser-210 and Se...
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.121173298
更新日期:2001-06-19 00:00:00
abstract::During protein synthesis, elongation factor G (EF-G) binds to the ribosome and promotes the step of translocation, a process in which tRNA moves from the A to the P site of the ribosome and the mRNA is advanced by one codon. By using three-dimensional cryo-electron microscopy, we have visualized EF-G in a ribosome-EF-...
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.95.11.6134
更新日期:1998-05-26 00:00:00
abstract::An enzymatic activity, having the properties expected of a B-specific host-controlled modification enzyme, has been purified from an extract of Escherichia coli strain B. This activity renders the unmodified replicative form of phage fd resistant to B-specific restriction and is only present in strains carrying intact...
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.63.2.556
更新日期:1969-06-01 00:00:00
abstract::Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions...
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.91.9.3739
更新日期:1994-04-26 00:00:00
abstract::The strong consistency of least squares estimates in multiple regression models with independent errors is obtained under minimal assumptions on the design and weak moment conditions on the errors. ...
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.75.7.3034
更新日期:1978-07-01 00:00:00